KOTAKE Yojiro

Researcher Information

URL

http://kaken.nii.ac.jp/d/r/90531963.ja.html

J-Global ID

• 201401029404613371

Research Interests

• ポリコーム   ポリコームタンパク   INK4遺伝子座   細胞老化   長鎖ノンコーディングRNA   ARF   細胞周期   癌化   転写制御   転写   p16   p53   ヒストン修飾   ノンコーディングRNA   精子幹細胞   ヒストンメチル化   ANRIL   エピジェネティクス   

Research Areas

• Life sciences / Molecular biology

Education

• 2001/04 - 2005/03  九州大学大学院  医学系学府  分子常態医学専攻
• 1999/04 - 2001/03  九州大学大学院  生物資源環境科学研究府  遺伝子資源工学専攻
• 1995/04 - 1999/03  Kyushu University  School of Agriculture  農芸化学科

Association Memberships

• バイオ治療法研究会   エピジェネティクス研究会   RNA学会   農芸化学会   癌学会   生化学会   分子生物学会   

Published Papers

• Histone H1.2 Represses the Transcription of the p16 Tumor Suppressor Gene

  Yojiro Kotake; Yoshinobu Tanigawa; Ryoka Tarumi

  Anticancer Research 43 (8) 3441 - 3446 2023/08 [Refereed]
  
• Elimination of Off-Target Effect by Chemical Modification of 5′-End of Small Interfering RNA

  Yasuo Shiohama; Ryosuke Fujita; Maika Sonokawa; Masaaki Hisano; Yojiro Kotake; Marija Krstic-Demonacos; Constantinos Demonacos; Gengo Kashiwazaki; Takashi Kitayama; Masayuki Fujii

  Nucleic Acid Therapeutics Mary Ann Liebert Inc 2159-3337 2022/04
• OIP5-AS1 Promotes Proliferation of Non-small-cell Lung Cancer and Head and Neck Squamous Cell Carcinoma Cells

  Yojiro Kotake; Natsumi Matsunaga; Takahiro Wakasaki; Ryotaro Okada

  Cancer Genomics & Proteomics. 18 (4) 543 - 548 2021/08 [Refereed]
  
• センス鎖のオフターゲット効果を低減するsiRNAの化学修飾

  塩浜康雄; 藤田崇史; 神武洋二郎; 藤井政幸

  近畿大学産業理工学部研究報告かやのもり (31) 1 - 7 2020/09 [Refereed]
  
• Long Noncoding RNA ANROC on the INK4 Locus Functions to Suppress Cell Proliferation

  Yojiro Kotake; Takeshi Tsuruda

  Cancer Genomics Proteomics . 17 (4) 425 - 430 2020/08 [Refereed]
  
• Telomerase inhibition, telomere attrition and proliferation arrest of cancer cells induced by phosphorothioate ASO-NLS conjugates targeting hTERC and siRNAs targeting hTERT.

  Irmina Diala; Yasuo Shiohama; Takashi Fujita; Yojiro Kotake; Constantinos Demonacos; Marija Krstic-Demonacos; Gianpiero Di Leva; Masayuki Fujii

  Nucleosides, nucleotides & nucleic acids 39 (1-3) 407 - 425 2020/04 [Refereed]
   

  Telomerase activity has been regarded as a critical step in cellular immortalization and carcinogenesis and because of this, regulation of telomerase represents an attractive target for anti-tumor specific therapeutics. Recently, one avenue of cancer research focuses on antisense strategy to target the oncogenes or cancer driver genes, in a sequence specific fashion to down-regulate the expression of the target gene. The protein catalytic subunit, human telomerase reverse transcriptase (hTERT) and the template RNA component (hTERC) are essential for telomerase function, thus theoretically, inhibition of telomerase activity can be achieved by interfering with either the gene expression of hTERT or the hTERC of the telomerase enzymatic complex. The present study showed that phosphorothioate antisense oligonucleotide (sASO)-nuclear localization signal (NLS) peptide conjugates targeting hTERC could inhibit telomerase activity very efficiently at 5 μM concentration but less efficiently at 1 μM concentration. On the other hand, siRNA targeting hTERT mRNA could strongly suppress hTERT expression at 200 nM concentration. It was also revealed that siRNA targeting hTERT could induce telomere attrition and then irreversible arrest of proliferation of cancer cells.
• Synthesis and Properties of Polycarbosilanes Having Lactose‐Derived Structures.

  Matsumoto K, Miyano T, Kotake Y.

  Journal of Polymer Science, Part A: Polymer Chemistry. 57(24):2420-2425, 2019. 2019/12 [Refereed]
  
• A novel compound, ferulic acid-bound resveratrol, induces the tumor suppressor gene p15 and inhibits the three-dimensional proliferation of colorectal cancer cells.

  Yuuga Sawata; Taiji Matsukawa; Satoshi Doi; Toshiyuki Tsunoda; Nagisa Arikawa; Natsumi Matsunaga; Koichiro Ohnuki; Senji Shirasawa; Yojiro Kotake

  Molecular and cellular biochemistry 462(1-2) (1-2) 25 - 31 2019/12 [Refereed]
   

  Resveratrol, a phytoalexin present in grapes and other edible foods, has been reported to have beneficial effects against various diseases including cancer. We previously reported that resveratrol and its derivative, caffeic acid-adducted resveratrol, selectively inhibit the three-dimensional (3D) proliferation of a human colorectal cancer cell line, HCT116 with activating KRAS mutation. Herein, we demonstrated that a novel compound, ferulic acid-bound resveratrol, also represses the 3D proliferation of HCT116 cells. We observed that resveratrol conjugated to two ferulic acids represses the 3D proliferation of HCT116 cells more strongly than resveratrol and resveratrol conjugated to one ferulic acid. Resveratrol conjugated to two ferulic acids also inhibited the 3D proliferation of MCF7 human breast cancer cells. We further uncovered that the resveratrol derivative increases the mRNA level of the tumor suppressor p15, a CDK inhibitor that functions as a brake of cell proliferation in HCT116 cells. These results imply that the resveratrol derivative represses 3D proliferation via increasing p15 expression in HCT116 cells.
• Long Noncoding RNA, ANRIL, Regulates the Proliferation of Head and Neck Squamous Cell Carcinoma.

  Natsumi Matsunaga; Takahiro Wakasaki; Ryuji Yasumatsu; Yojiro Kotake

  Anticancer research 39(8) (8) 4073 - 4077 2019/08 [Refereed]
   

  BACKGROUND/AIM: ANRIL is a long noncoding RNA located on INK4 locus, which encodes p15 and p16 that cause G1 phase arrest in the cell cycle. ANRIL positively regulates proliferation of several kinds of cancer cells such as lung and gastric cancers. This study, examined the effect of ANRIL in head and neck squamous cell carcinoma cells. MATERIALS AND METHODS: Cells were transfected with siRNA oligonucleotides targeting ANRIL. Transfected cells were subjected to cell-cycle and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. RESULTS: Depletion of ANRIL increased p15 mRNA in FaDu cells, and p15 and p16 mRNA in CAL27 cells and inhibited proliferation of these cells. Cell cycle analysis showed that depletion of ANRIL caused arrest at the G1 phase of the cell cycle. CONCLUSION: ANRIL promotes G1 phase progression by repressing p15 and p16, and thus promotes FaDu and CAL27 cell proliferation.
• siRNAによる変異癌遺伝子KRAS（G12D）の選択的発現制御

  塩浜康雄; 藤田崇史; 神武洋二郎; 岡田斉; 藤井政幸

  近畿大学産業理工学部研究報告かやのもり (30) 1 - 7 2019 [Refereed]
  
• Selective Regulation of Mutant Oncogene KRAS (G12D) by Gapmer Antisense Nucleic Acids

  Shiohama Yasuo

  Reports of School of Humanity-Oriented Science and Engineering, Kinki University 近畿大学産業理工学部 (29) 1 - 5 1349-5801 2018/11 

  〈Abstract〉KRAS mutation is positive in 45% of colon cancer patients, 35% of lung cancer patients, 95% of pancreas cancer patients, and 15% of melanoma patients and the patients do not benefit from anti-epidermal growth factor receptor (EGFR) chemotherapy and antibody therapy to have poor prognosis for survival. KRAS mutations in codons 12 and 13 were present approximately in 40% of colorectal cancers. It is highly challenging to target mutant KRAS gene by synthetic small nucleic acids and can be a breakthrough for undruggable cancers.In the present study, we investigated silencing efficiencies of mutant KRAS(G12D) gene by gapmer antisense oligonucleotides (ASO) using HeLa with wild type KRAS and PK-45H with G12D mutation in both alleles. ASOs targeting mutant KRAS (G12D) with 11nt and 9nt phosphorothioate gap silenced KRAS(G12D) expression in 81% and 73% efficiency in PK-45H, respectively but affected very little on the wild type KRAS expression in HeLa.
• A novel resveratrol derivative selectively inhibits the proliferation of colorectal cancer cells with KRAS mutation

  Haruna Okamoto; Taiji Matsukawa; Satoshi Doi; Toshiyuki Tsunoda; Yuuga Sawata; Madoka Naemura; Koichiro Ohnuki; Senji Shirasawa; Yojiro Kotake

  Molecular and Cellular Biochemistry Springer New York LLC 442 (1-2) 39 - 45 1573-4919 2018/05 [Refereed]
   

  Resveratrol is a polyphenolic compound in many edible foods including grapes, peanuts, and berries. Several studies have revealed the beneficial effects of resveratrol against various diseases such as heart disease, diabetes, obesity, neurological disorders, and cancer. A recent study showed that resveratrol inhibits the proliferation of HCT116 human colorectal cancer cells in three-dimensional culture (3DC) via induction of luminal apoptosis in HCT116 cell spheroids. In this study, we showed that a novel compound, caffeic acid-adducted resveratrol, has a stronger inhibitory effect on the growth of HCT116 cell spheroids in 3DC than resveratrol. It showed almost the same inhibitory efficacy as 5-fluorouracil, a conventional anticancer drug. We further showed that the resveratrol derivative did not affect the growth of HKe3 cell spheroids derived from HCT116 cells by disruption of the activating mutant KRAS gene. These results suggest that the resveratrol derivative inhibits the growth of HCT116 cell spheroids via inhibition of an oncogenic KRAS-mediated signaling pathway.
• The long noncoding RNA OIP5-AS1 is involved in the regulation of cell proliferation

  Madoka Naemura; Masahide Kuroki; Toshiyuki Tsunoda; Nagisa Arikawa; Yuuga Sawata; Senji Shirasawa; Yojiro Kotake

  Anticancer Research International Institute of Anticancer Research 38 (1) 77 - 81 1791-7530 2018/01 [Refereed]
   

  Background/Aim: OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) is a long noncoding RNA located on human chromosome 15q15.1 and transcribed in the opposite direction to OIP5. Here, we report that OIP5-AS1 is involved in regulating cell proliferation. Materials and Methods: HeLa cells were transfected with OIP5-AS1-targeting siRNA oligonucleotides and anti-sense oligonucleotides. The cells were harvested 72 h after transfection and subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and cell-cycle and apoptosis analysis. Results: OIP5-AS1 was expressed at a lower level in cells harbouring an oncogenic kirsten rat sarcoma viral oncogene homolog (K-RAS) mutation than in cells expressing wild-type K-RAS. Silencing OIP5-AS1 with siRNA oligonucleotides or anti-sense oligonucleotides reduced HeLa cell proliferation. Apoptosis and cell-cycle analysis showed that silencing OIP5-AS1 did not cause apoptosis, but did cause G2/M phase cell-cycle arrest. Conclusion: These results suggest that OIP5-AS1 positively regulates cell proliferation by promoting G2/M phase progression.
• Homeobox Transcription Factor NKX2-1 Promotes Cyclin D1 Transcription in Lung Adenocarcinomas

  Masanori Harada; Satoshi Sakai; Tatsuya Ohhata; Kyoko Kitagawa; Masashi Mikamo; Koji Nishimoto; Chiharu Uchida; Hiroyuki Niida; Yojiro Kotake; Haruhiko Sugimura; Takafumi Suda; Masatoshi Kitagawa

  MOLECULAR CANCER RESEARCH AMER ASSOC CANCER RESEARCH 15 (10) 1388 - 1397 1541-7786 2017/10 [Refereed]
   

  The known oncogene cyclin D1 (CCND1) participates in progression of the cell cycle from G1 to S-phase. Expression of cyclin D1 is frequently promoted in multiple human cancers including non-small cell lung cancer (NSCLC). However, a relationship between cyclinD1expression and the prognosis ofNSCLChas not been confirmed. NKX2-1 is a homeobox transcription factor involved in pulmonary development as a differentiation-promoting factor. In NSCLC, it acts as a metastasis suppressor and correlates with a good prognosis. Here, NKX2-1-binding motifs were identified in the cyclin D1 promoter, but it has not been clarified whether NKX2-1 is involved in cyclin D1 expression in NSCLC. To shed light on this issue, endogenous NKX2-1 was depleted in NSCLC cell lines, which resulted in decreased cyclin D1 mRNA and protein. In contrast, forced overexpression of NKX2-1 increased cyclin D1 levels. Moreover, NKX2-1 directly bound to the cyclin D1 promoter and enhanced its activity. Finally, using human NSCLC clinical specimens, it was determined that both NKX2-1 protein and mRNA were significantly correlated with cyclin D1 expression status in adenocarcinomas. These results indicate that NKX2-1 directly and positively regulates transcription of cyclin D1. Finally, expression of NKX2-1, but not cyclin D1, was significantly associated with metastatic incidence as an independent good prognostic factor of adenocarcinoma. (C) 2017 AACR.
• Silencing of BCR/ABL Chimeric Gene in Human Chronic Myelogenous Leukemia Cell Line K562 by siRNA-Nuclear Export Signal Peptide Conjugates

  Yasuhiro Shinkai; Shinichi Kashihara; Go Minematsu; Hirofumi Fujii; Madoka Naemura; Yojiro Kotake; Yasutaka Morita; Koichiro Ohnuki; Alesya A. Fokina; Dmitry A. Stetsenko; Vyacheslav V. Filichev; Masayuki Fujii

  NUCLEIC ACID THERAPEUTICS MARY ANN LIEBERT, INC 27 (3) 168 - 175 2159-3337 2017/06 [Refereed]
   

  Herein we described the synthesis of siRNA-NES (nuclear export signal) peptide conjugates by solid phase fragment coupling and the application of them to silencing of bcr/abl chimeric gene in human chronic myelogenous leukemia cell line K562. Two types of siRNA-NES conjugates were prepared, and both sense strands at 5' ends were covalently linked to a NES peptide derived from TFIIIA and HIV-1 REV, respectively. Significant enhancement of silencing efficiency was observed for both of them. siRNA-TFIIIA NES conjugate suppressed the expression of BCR/ABL gene to 8.3% at 200nM and 11.6% at 50 nM, and siRNA-HIV-1REV NES conjugate suppressed to 4.0% at 200nM and 6.3% at 50 nM, whereas native siRNA suppressed to 36.3% at 200nM and 30.2% at 50 nM. We could also show complex of siRNA-NES conjugate and designed amphiphilic peptide peptide beta 7 could be taken up into cells with no cytotoxicity and showed excellent silencing efficiency. We believe that the complex siRNA-NES conjugate and peptideb7 is a promising candidate for in vivo use and therapeutic applications.
• Y-box Binding Protein 1 Is Involved in Regulating the G(2)/M Phase of the Cell Cycle

  Yojiro Kotake; Nagisa Arikawa; Keiichiro Tahara; Hiroaki Maru; Madoka Naemura

  ANTICANCER RESEARCH INT INST ANTICANCER RESEARCH 37 (4) 1603 - 1608 0250-7005 2017/04 [Refereed]
   

  Background/Aim: The transcription factor Y-box-binding protein 1 (YB1) is overexpressed in many types of human cancers. YB1 regulates the G(1) phase of the cell cycle by controlling transcription of G(1) regulators. Here, we report that YB1 is also involved in regulating G(2)/M phase. Materials and Methods: YB1-depleted TKO cells were subjected to quantitative reverse transcription-polymerase chain reaction and cell-cycle analysis. RNA immuno-precipitation (RIP)-chip assay was performed using anti-YB1 antibodies. Precipitated RNAs were subjected to microarray analysis. Results: Silencing YB1 inhibited the proliferation of TKO cells, which lost the machinery required for G(1) phase arrest. Cell-cycle analysis showed that silencing YB1 caused G(2)/M phase cellcycle arrest. RIP-chip assay showed that YB1 associated with mRNA of multiple cell-cycle-related genes, including G(2)/M phase regulators. Conclusion: YB1 positively regulates not only the G(1) phase but also G(2)/M phase by regulating multiple cell-cycle-related genes.
• Gene Silencing by Major Groove Modified siRNAs

  新貝恭広; 苗村円佳; 神武洋二郎; 藤井政幸

  近畿大学産業理工学部研究報告かやのもり 近畿大学産業理工学部 (26) 1 - 10 1349-5801 2017 [Refereed]
   

  Small interfering RNA (siRNA) induces RNA interference by forming RNA induced silencing complex (RISC). From a therapeutic point of view, chemical modifications and conjugations of siRNA are powerful strategies to improve their properties toward clinical applications. We can access to siRNA molecules from hydroxyl groups, phosphate backbone, and major groove side and minor groove side of nucleobases. We need to know proper moieties at proper positions for chemical modifications to construct an optimized structure of siRNA. In the present study, we synthesized and evaluated 10 types of siRNAs bearing C5-modified T. All the siRNAs modified in the antisense strand showed reduced silencing efficiencies. It is to be noted the modified positions which intensively reduced silencing efficiencies are well consistent with the positions having major kinks and turns in the crystal structure of guide strandim & Ago2. On the other hand, modification of the sense strand caused less damage to silencing of siRNA and no damage was observed for the modification at s8.
• Long Noncoding RNA PANDA Positively Regulates Proliferation of Osteosarcoma Cells

  Yojiro Kotake; Taiki Goto; Madoka Naemura; Yasutoshi Inoue; Haruna Okamoto; Keiichiro Tahara

  ANTICANCER RESEARCH INT INST ANTICANCER RESEARCH 37 (1) 81 - 85 0250-7005 2017/01 [Refereed]
   

  Background: A long noncoding RNA, p21-associated ncRNA DNA damage-activated (PANDA), associates with nuclear transcription factor Y subunit alpha (NF-YA) and inhibits its binding to promoters of apoptosis-related genes, thereby repressing apoptosis in normal human fibroblasts. Here, we show that PANDA is involved in regulating proliferation in the U2OS human osteosarcoma cell line. Materials and Methods: U2OS cells were transfected with siRNAs against PANDA 72 h later and they were subjected to reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and cell-cycle analysis. Results: PANDA was highly expressed in U2OS cells, and its expression was induced by DNA damage. Silencing PANDA caused arrest at the G(1) phase of the cell cycle, leading to inhibition of cell proliferation. Quantitative RT-PCR showed that silencing PANDA increased mRNA levels of the cyclin-dependent kinase inhibitor p18, which caused G(1) phase arrest. Conclusion: These results suggest that PANDA promotes G(1)-S transition by repressing p18 transcription, and thus promotes U2OS cell proliferation.
• Oncogenic Ras influences the expression of multiple lncRNAs

  Yojiro Kotake; Madoka Naemura; Kyoko Kitagawa; Hiroyuki Niida; Toshiyuki Tsunoda; Senji Shirasawa; Masatoshi Kitagawa

  CYTOTECHNOLOGY SPRINGER 68 (4) 1591 - 1596 0920-9069 2016/08 [Refereed]
   

  Recent ultrahigh-density tiling array and large-scale transcriptome analysis have revealed that large numbers of long non-coding RNAs (lncRNAs) are transcribed in mammals. Several lncRNAs have been implicated in transcriptional regulation, organization of nuclear structure, and post-transcriptional processing. However, the regulation of expression of lncRNAs is less well understood. Here, we show that the exogenous and endogenous expression of an oncogenic form of small GTPase Ras (called oncogenic Ras) decrease the expression of lncRNA ANRIL (antisense non-coding RNA in the INK4 locus), which is involved in the regulation of cellular senescence. We also show that forced expression of oncogenic Ras increases the expression of lncRNA PANDA (p21 associated ncRNA DNA damage activated), which is involved in the regulation of apoptosis. Microarray analysis demonstrated that expression of multiple lncRNAs fluctuated by forced expression of oncogenic Ras. These findings indicate that oncogenic Ras regulates the expression of a large number of lncRNAs including functional lncRNAs, such as ANRIL and PANDA.
• Gene Silencing by Chemically Modified Small Interfering RNA (siRNA)

  新貝 恭広; 柏原 慎一; 藤井 啓史; 峰松 剛; 吉永 尚平; 苗村 円佳; 神武 洋二郎; 藤井 政幸

  近畿大学産業理工学部研究報告 近畿大学産業理工学部 (24) 1 - 5 1349-5801 2016/07 

  For clinical applications of small interfering RNA (siRNA), chemical structure of siRNA should be optimized to be taken up into cells effectively, resistant to nuclease digestion, incorporated into RNA induced silencing complex (RISC) rapidly and correctly. They should also have minimized off-target effect and maximized turn over number. In this study, we investigated RNA interference (RNAi) efficiencies of siRNAs bearing 5'-amino-5'-deoxythymidine (T*) at 5'-end. The results showed that T* at the 5'-end of the sense strand did not interfere the processes of RISC loading complex (RLC) formation, loading to RISC or cleavage of the passenger strand by human argonaute2 (hAgo2) at all. On the other hand, T* at the 5'-end of the antisense strand gave a fatal damage to siRNA to show almost no silencing effect probably because RISC was destabilized by an electrostatic repulsion between the cationic charge of the ammonium group of T* and the cationic residues in MID domain pocket of hAgo2. These results strongly suggest that a modification of 5'-end of a sense strand with T* will suppress an off-target effect.
• Long Non-coding RNA, PANDA, Contributes to the Stabilization of p53 Tumor Suppressor Protein

  Yojiro Kotake; Kyoko Kitagawa; Tatsuya Ohhata; Satoshi Sakai; Chiharu Uchida; Hiroyuki Niida; Madoka Naemura; Masatoshi Kitagawa

  ANTICANCER RESEARCH INT INST ANTICANCER RESEARCH 36 (4) 1605 - 1611 0250-7005 2016/04 [Refereed]
   

  Background: P21-associated noncoding RNA DNA damage-activated (PANDA) is induced in response to DNA damage and represses apoptosis by inhibiting the function of nuclear transcription factor Y subunit alpha (NF-YA) transcription factor. Herein, we report that PANDA affects regulation of p53 tumor-suppressor protein. Materials and Methods: U2OS cells were transfected with PANDA siRNAs. At 72 h post-transfection, cells were subjected to immunoblotting and quantitative reverse transcription-polymerase chain reaction. Results: Depletion of PANDA was associated with decreased levels of p53 protein, but not p53 mRNA. The stability of p53 protein was markedly reduced by PANDA silencing. Degradation of p53 protein by silencing PANDA was prevented by treatment of MG132, a proteasome inhibitor. Moreover, depletion of PANDA prevented accumulation of p53 protein, as a result of DNA damage, induced by the genotoxic agent etoposide. Conclusion: These results suggest that PANDA stabilizes p53 protein in response to DNA damage, and provide new insight into the regulatory mechanisms of p53.
• ANRIL regulates the proliferation of human colorectal cancer cells in both two- and three-dimensional culture

  Madoka Naemura; Toshiyuki Tsunoda; Yasutoshi Inoue; Haruna Okamoto; Senji Shirasawa; Yojiro Kotake

  MOLECULAR AND CELLULAR BIOCHEMISTRY SPRINGER 412 (1-2) 141 - 146 0300-8177 2016/01 [Refereed]
   

  ANRIL is a long noncoding RNA transcribed from the INK4 locus that encodes three tumor suppressor genes, p15, p16, and ARF. Previous studies demonstrated that ANRIL represses p15 and p16, which positively regulate the pRB pathway, leading to repression of cellular senescence of human normal fibroblasts. However, the role of ANRIL in cancer cell proliferation is less well understood. Here we report that ANRIL is involved in the proliferation of colorectal cancer HCT116 cells in two-and three-dimensional culture. Silencing ANRIL by both transfection with small interfering RNA and retrovirally produced small hairpin RNA reduced HCT116 cell proliferation in both two-and three-dimensional culture. HCT116 cells depleted for ANRIL were arrested in the S phase of cell cycle. Notably, silencing ANRIL did not result in the activation of expression of the INK4 locus. These results suggest that ANRIL positively regulates the proliferation of HCT116 cells in two-and three-dimensional culture in a p15/p16-pRB pathway-independent manner.
• LONG NONCODING RNA ANRIL PROMOTES PROLIFERATION OF CANCER CELLS

  Madoka Naemura; Chihiro Murasaki; Yasutoshi Inoue; Haruna Okamoto; Yojiro Kotake

  Proceeding of Joint International Symposium on「Regional Revitalization and Innovation for Social Contribution」 and and「e-ASIA Functional Materials and Biomass Utilization 2015」 54  2015/11 [Refereed]
  
• THE FUNCTIONAL ANALYSIS OF NOVEL LONG NON-CODING RNA INVOLVED IN CARCINOGENESIS

  Yasutoshi Inoue; Madoka Naemura; Chihiro Murasaki; Haruna Okamoto; Yojiro Kotake

  Proceeding of Joint International Symposium on「Regional Revitalization and Innovation for Social Contribution」 and and「e-ASIA Functional Materials and Biomass Utilization 2015」 53  2015/11 [Refereed]
  
• Long Noncoding RNA ANRIL Regulates Proliferation of Non-small Cell Lung Cancer and Cervical Cancer Cells

  Madoka Naemura; Chihiro Murasaki; Yasutoshi Inoue; Haruna Okamoto; Yojiro Kotake

  ANTICANCER RESEARCH INT INST ANTICANCER RESEARCH 35 (10) 5377 - 5382 0250-7005 2015/10 [Refereed]
   

  Background: Long noncoding RNA ANRIL (antisense non-coding RNA in the INK4 locus) represses p15 and p16, which induce cell-cycle arrest at G(1) phase, leading to enhanced cell proliferation of normal fibroblasts. Herein we report that ANRIL is also involved in the regulation of cancer-cell proliferation. Materials and Methods: HeLa and H1299 cells were transfected with ANRIL siRNAs. At 72 h post-transfection, cells were subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and cell-cycle analysis. Results: qRT-PCR showed that ANRIL is highly expressed in these cancer cells compared to normal fibroblasts. Depletion of ANRIL increased p15 expression, with no impact on p16 or ARF (alternative reading frame) expression, and caused cell-cycle arrest at the G(2)/M phase, leading to inhibition of proliferation of H1299 and HeLa cells. Conclusion: ANRIL positively regulates the proliferation of cancer cells, such as H1299 and HeLa cells, via regulating p15 and other genes related to G(2)/M phase control.
• Transcriptional Regulation of the p16 Tumor Suppressor Gene

  Yojiro Kotake; Madoka Naemura; Chihiro Murasaki; Yasutoshi Inoue; Haruna Okamoto

  ANTICANCER RESEARCH INT INST ANTICANCER RESEARCH 35 (8) 4397 - 4401 0250-7005 2015/08 [Refereed]
   

  The p16 tumor suppressor gene encodes a specific inhibitor of cyclin-dependent kinase (CDK) 4 and 6 and is found altered in a wide range of human cancers. p16 plays a pivotal role in tumor suppressor networks through inducing cellular senescence that acts as a barrier to cellular transformation by oncogenic signals. p16 protein is relatively stable and its expression is primary regulated by transcriptional control. Polycomb group (PcG) proteins associate with the p16 locus in a long non-coding RNA, ANRIL-dependent manner, leading to repression of p16 transcription. YB1, a transcription factor, also represses the p16 transcription through direct association with its promoter region. Conversely, the transcription factors Ets1/2 and histone H3K4 methyltransferase MLL1 directly bind to the p16 locus and mediate p16 induction during replicative and premature senescence. In the present review, we discuss the molecular mechanisms by which these factors regulate p16 transcription.
• Regulation of Prb and P53 pathways by the long noncoding RNAs ANRIL, lincrna-p21, lincrna-RoR, and panda

  Yojiro Kotake; Masatoshi Kitagawa

  Long Noncoding RNAs Structures and Functions Springer Japan 175 - 189 2015/01 [Refereed]
   

  Retinoblastoma protein (pRB) and p53 pathways play a key role in controlling the cell cycle and apoptosis in response to oncogenic insults and DNA damage. Disruption of these pathways deregulates the control of cell proliferation and represents a common event in the development of most types of human cancer. Recent studies have revealed that several long noncoding RNAs (lncRNAs) are involved in the regulation of pRB and p53 pathways, through transcriptional and translational control of target genes. In this chapter, we focus on four lncRNAs: ANRIL, lincRNA-p21, lincRNA-RoR, and PANDA. These lncRNAs are involved in the pRB and p53 pathways. ANRIL associates with and recruits polycomb proteins to repress the transcription of cyclin-dependent kinase (CDK) inhibitor p15 and p16 genes, resulting in the repression of pRB function. lincRNA-p21, lincRNA-RoR, and PANDA are induced by p53 in response to DNA damage and regulate apoptosis. We discuss the involvement of ANRIL, lincRNA-p21, lincRNA-RoR, and PANDA in cellular functions through the pRB and p53 pathways, and the molecular mechanisms by which these lncRNAs regulate the expression of target genes.
• Regulation of cell proliferation and apoptosis by long noncoding RNA, ANRIL and PANDA

  Yojiro Kotake; Madoka Naemura; Chihiro Murasaki

  Seikagaku Japanese Biochemical Society 87 (2) 230 - 233 2189-0544 2015 [Refereed]
  
• Efficient transfection of siRNA by designed peptides.

  Kayano H; Takashina A; Naemura M; Kotake Y; Morita Y; Fujii M

  Proceedings of the 41st International Symposium on Nucleic Acids Chemistry. 374 - 375 2014/09 [Refereed]
  
• YB-1 promotes transcription of cyclin D1 in human non-small-cell lung cancers

  Masanori Harada; Yojiro Kotake; Tatsuya Ohhata; Kyoko Kitagawa; Hiroyuki Niida; Shun Matsuura; Kazuhito Funai; Haruhiko Sugimura; Takafumi Suda; Masatoshi Kitagawa

  GENES TO CELLS WILEY-BLACKWELL 19 (6) 504 - 516 1356-9597 2014/06 [Refereed]
   

  Cyclin D1, an oncogenic G1 cyclin, and YB-1, a transcription factor involved in cell growth, are both over-expressed in several human cancers. In human lung cancer, the functional association between YB-1 and cyclin D1 has never been elucidated. In this study, we show YB-1 is involved in the transcription of cyclin D1 in human lung cancer. Depletion of endogenous YB-1 by siRNA inhibited progression of G1 phase and down-regulated both the protein and mRNA levels of cyclin D1 in human lung cancer cells. Forced over-expression of YB-1 with a cyclin D1 reporter plasmid increased luciferase activity, and ChIP assay results showed YB-1 bound to the cyclin D1 promoter. Moreover, the amount of YB-1 mRNA positively correlated with cyclin D1 mRNA levels in clinical non-small-cell lung cancer (NSCLC) specimens. Immunohistochemical analysis also indicated YB-1 expression correlated with cyclin D1 expression in NSCLC specimens. In addition, most of the cases expressing both cyclin D1 and CDC6, another molecule controlled by YB-1, had co-existing YB-1 over-expression. Together, our results suggest that aberrant expression of both cyclin D1 and CDC6 by YB-1 over-expression may collaboratively participate in lung carcinogenesis.
• Yb-1 Promotes Transcription Of Cyclin D1 In Human Non-Small-Cell Lung Cancers

  M. Harada; Y. Kotake; T. Ohhata; K. Kitagawa; H. Niida; S. Matsuura; K. Funai; H. Sugimura; T. Suda; M. Kitagawa

  AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE AMER THORACIC SOC 189 (6) 504 - 516 1073-449X 2014 [Refereed]
  
• Cell cycle regulation by long non-coding RNAs

  Masatoshi Kitagawa; Kyoko Kitagawa; Yojiro Kotake; Hiroyuki Niida; Tatsuya Ohhata

  CELLULAR AND MOLECULAR LIFE SCIENCES SPRINGER BASEL AG 70 (24) 4785 - 4794 1420-682X 2013/12 [Refereed]
   

  The mammalian cell cycle is precisely controlled by cyclin-dependent kinases (CDKs) and related pathways such as the RB and p53 pathways. Recent research on long non-coding RNAs (lncRNAs) indicates that many lncRNAs are involved in the regulation of critical cell cycle regulators such as the cyclins, CDKs, CDK inhibitors, pRB, and p53. These lncRNAs act as epigenetic regulators, transcription factor regulators, post-transcription regulators, and protein scaffolds. These cell cycle-regulated lncRNAs mainly control cellular levels of cell cycle regulators via various mechanisms, and may provide diversity and reliability to the general cell cycle. Interestingly, several lncRNAs are induced by DNA damage and participate in cell cycle arrest or induction of apoptosis as DNA damage responses. Therefore, deregulations of these cell cycle regulatory lncRNAs may be involved in tumorigenesis, and they are novel candidate molecular targets for cancer therapy and diagnosis.
• YB1 binds to and represses the p16 tumor suppressor gene

  Yojiro Kotake; Yuichi Ozawa; Masanori Harada; Kyoko Kitagawa; Hiroyuki Niida; Yasutaka Morita; Kenji Tanaka; Takafumi Suda; Masatoshi Kitagawa

  GENES TO CELLS WILEY-BLACKWELL 18 (11) 999 - 1006 1356-9597 2013/11 [Refereed]
   

  Y box binding protein 1 (YB1) has multiple functions associated with drug resistance, cell proliferation and metastasis through transcriptional and translational regulation. Increased expression of YB1 is closely related to tumor growth and aggressiveness. We showed that YB1 protein levels were decreased through replicative and premature senescence and were correlated with increased expression levels of p16(INK4A) tumor suppressor gene. Depletion of YB1 was associated with increased levels of p16 in human and murine primary cells. Forced expression of YB1 in mouse embryonic fibroblasts resulted in decreased expression of p16 and increased cell proliferation. Senescence-associated expression of -galactosidase was repressed in YB1-over-expressing cells. Chromatin immunoprecipitation assays showed that YB1 directly associates with the p16 promoter. Taken together, all our findings indicate that YB1 directly binds to and represses p16 transcription, subsequently resulting in the promotion of cell growth and prevention of cellular senescence.
• Long Non-Coding RNAs Involved in Cancer Development and Cell Fate Determination

  Masatoshi Kitagawa; Yojiro Kotake; Tatsuya Ohhata

  CURRENT DRUG TARGETS BENTHAM SCIENCE PUBL LTD 13 (13) 1616 - 1621 1389-4501 2012/12 [Refereed]
   

  The possible physiological significance of long non-coding RNAs (lncRNAs) has only recently been recognized. Technical innovations such as the super high-resolution tiling array and deep sequencing technology have indicated their importance. It has been proposed that lncRNAs such as HOTAIR are involved in the recruitment of chromatin modifiers to the target genes. The lncRNA ANRIL has been reported to be associated with a Polycomb complex, recruiting it to the target gene INK4 locus where it suppresses transcription via histone modification. Other lncRNAs such as Kcnq1ot1, AIR and Xist have also been found to recruit chromatin modifiers to their target loci. In this review, we discuss the function of lncRNAs such as HOTAIR, ANRIL, Kcnq1ot1, and Xist which recruit chromatin modifiers to target genes and discuss their involvement in cancer development and aggressiveness, and other cell fate determination.
• Chk1 phosphorylates the tumour suppressor Mig-6, regulating the activation of EGF signalling

  Ning Liu; Masaki Matsumoto; Kyoko Kitagawa; Yojiro Kotake; Sayuri Suzuki; Senji Shirasawa; Keiichi I. Nakayama; Makoto Nakanishi; Hiroyuki Niida; Masatoshi Kitagawa

  EMBO JOURNAL NATURE PUBLISHING GROUP 31 (10) 2365 - 2377 0261-4189 2012/05 [Refereed]
   

  The tumour suppressor gene product Mig-6 acts as an inhibitor of epidermal growth factor (EGF) signalling. However, its posttranslational modifications and regulatory mechanisms have not been elucidated. Here, we investigated the phosphorylation of human Mig-6 and found that Chk1 phosphorylated Mig-6 in vivo as well as in vitro. Moreover, EGF stimulation promoted phosphorylation of Mig-6 without DNA damage and the phosphorylation was inhibited by depletion of Chk1. EGF also increased Ser280-phosphorylated Chk1, a cytoplasmic-tethering form, via PI3K pathway. Mass spectrometric analyses suggested that Ser 251 of Mig-6 was a major phosphorylation site by Chk1 in vitro and in vivo. Substitution of Ser 251 to alanine increased inhibitory activity of Mig-6 against EGF receptor (EGFR) activation. Moreover, EGF-dependent activation of EGFR and cell growth were inhibited by Chk1 depletion, and were rescued by co-depletion of Mig-6. Our results suggest that Chk1 phosphorylates Mig-6 on Ser 251, resulting in the inhibition of Mig-6, and that Chk1 acts as a positive regulator of EGF signalling. This is a novel function of Chk1. The EMBO Journal (2012) 31, 2365-2377. doi: 10.1038/emboj.2012.88; Published online 13 April 2012
• The Amelioration of Renal Damage in Skp2-Deficient Mice Canceled by p27 (Kip1) Deficiency in Skp2(-/-) p27(-/-) Mice

  Sayuri Suzuki; Hirotaka Fukasawa; Taro Misaki; Akashi Togawa; Naro Ohashi; Kyoko Kitagawa; Yojiro Kotake; Ning Liu; Hiroyuki Niida; Keiko Nakayama; Keiichi I. Nakayama; Tatsuo Yamamoto; Masatoshi Kitagawa

  PLOS ONE PUBLIC LIBRARY SCIENCE 7 (4) 1 - 9 1932-6203 2012/04 [Refereed]
   

  SCF-Skp2 E3 ubiquitin ligase (Skp2 hereafter) targets several cell cycle regulatory proteins for degradation via the ubiquitin-dependent pathway. However, the target-specific physiological functions of Skp2 have not been fully elucidated in kidney diseases. We previously reported an increase in Skp2 in progressive nephropathy and amelioration of unilateral ureteral obstruction (UUO) renal injury associated with renal accumulation of p27 in Skp2(-/-) mice. However, it remains unclear whether the amelioration of renal injury in Skp2(-/-) mice is solely caused by p27 accumulation, since Skp2 targets several other proteins. Using Skp2(-/-) p27(-/-) mice, we investigated whether Skp2 specifically targets p27 in the progressive nephropathy mediated by UUO. In contrast to the marked suppression of UUO renal injury in Skp2(-/-) mice, progression of tubular dilatation associated with tubular epithelial cell proliferation and tubulointerstitial fibrosis with increased expression of collagen and alpha-smooth muscle actin were observed in the obstructed kidneys in Skp2(-/-) p27(-/-) mice. No significant increases in other Skp2 target proteins including p57, p130, TOB1, cyclin A and cyclin D1 were noted in the UUO kidney in Skp2(-/-) mice, while p21, c-Myc, b-Myb and cyclin E were slightly increased. Contrary to the ameliorated UUO renal injure by Skp2-deficiency, the amelioration was canceled by the additional p27-deficiency in Skp2(-/-) p27(-/-) mice. These findings suggest a pathogenic role of the reduction in p27 targeted by Skp2 in the progression of nephropathy in UUO mice.
• Up-regulation of Cks1 and Skp2 with TNF alpha/NF-kappa B signaling in chronic progressive nephropathy

  Sayuri Suzuki; Hirotaka Fukasawa; Taro Misaki; Akashi Togawa; Naro Ohashi; Kyoko Kitagawa; Yojiro Kotake; Hiroyuki Niida; Akira Hishida; Tatsuo Yamamoto; Masatoshi Kitagawa

  GENES TO CELLS WILEY-BLACKWELL 16 (11) 1110 - 1120 1356-9597 2011/11 [Refereed]
   

  The cyclin-dependent kinase (CDK) inhibitor p27 level is associated with progression of renal damage. We previously reported that mRNA of Skp2, a component of Skp/Cullin/F-box (SCF)-ubiquitin ligase which targets to p27, was increased in unilateral ureteral obstructive kidneys in mice and that the nephritis was attenuated in Skp2-deficient mice. However, the details have not been fully clarified. Here, we found that not only Skp2 but also cdc kinase subunit 1 (Cks1), an essential cofactor for the SCF-Skp2 ubiquitin ligase in targeting p27, was increased in another chronic progressive model, anti-thymocyte serum (ATS) rat nephropathy. After induction of ATS nephropathy, Skp2(+)/Cks1(+)/Ki67(+) tubular epithelial cell numbers increased, and p27(+) tubular epithelial cells decreased transiently. Moreover, we found that TNF alpha was involved in expression of both Skp2 and Cks1 in NRK cell line as well as the in ATS nephropathy. Nuclear accumulations of NF-kappa B subunits RelB and p52 were increased in the tubular epithelial cells of the nephritic kidney. Both Skp2 and Cks1 were colocalized with RelB in these cells. These data suggest that both Skp2 and Cks1 are up-regulated by the TNF alpha-RelB/p52 pathway in the early stages of renal damage and are collaboratively involved in down-regulation of p27 in proliferative tubular dilation and the progression of chronic nephropathy.
• Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters

  Tiffany Hung; Yulei Wang; Michael F. Lin; Ashley K. Koegel; Yojiro Kotake; Gavin D. Grant; Hugo M. Horlings; Nilay Shah; Christopher Umbricht; Pei Wang; Yu Wang; Benjamin Kong; Anita Langerod; Anne-Lise Borresen-Dale; Seung K. Kim; Marc van de Vijver; Saraswati Sukumar; Michael L. Whitfield; Manolis Kellis; Yue Xiong; David J. Wong; Howard Y. Chang

  NATURE GENETICS NATURE PUBLISHING GROUP 43 (7) 621 - U196 1061-4036 2011/07 [Refereed]
   

  Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR-validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.
• Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene

  Y. Kotake; T. Nakagawa; K. Kitagawa; S. Suzuki; N. Liu; M. Kitagawa; Y. Xiong

  ONCOGENE NATURE PUBLISHING GROUP 30 (16) 1956 - 1962 0950-9232 2011/04 [Refereed]
   

  A 42 kb region on human chromosome 9p21 encodes for three distinct tumor suppressors, p16(INK4A), p14(ARF) and p15(INK4B), and is altered in an estimated 30-40% of human tumors. The expression of the INK4A-ARF-INK4B gene cluster is silenced by polycomb during normal cell growth and is activated by oncogenic insults and during aging. How the polycomb is recruited to repress this gene cluster is unclear. Here, we show that expression of oncogenic Ras, which stimulates the expression of p15(INK4B) and p(16INK4A), but not p14ARF, inhibits the expression of ANRIL (antisense non-coding RNA in the INK4 locus), a 3.8 kblong non-coding RNA expressed in the opposite direction from INK4A-ARF-INK4B. We show that the p15(INK4B) locus is bound by SUZ12, a component of polycomb repression complex 2 (PRC2), and is H3K27-trimethylated. Notably, depletion of ANRIL disrupts the SUZ12 binding to the p15(INK4B) locus, increases the expression of p15(INK4B), but not p16(INK4A) or p14(ARF), and inhibits cellular proliferation. Finally, RNA immunoprecipitation demonstrates that ANRIL binds to SUZ12 in vivo. Collectively, these results suggest a model in which ANRIL binds to and recruits PRC2 to repress the expression of p15INK4B locus. Oncogene (2011) 30, 1956-1962; doi: 10.1038/onc.2010.568; published online 13 December 2010
• p53 Binds to and Is Required for the Repression of Arf Tumor Suppressor by HDAC and Polycomb

  Yaxue Zeng; Yojiro Kotake; Xin-Hai Pei; Matthew D. Smith; Yue Xiong

  CANCER RESEARCH AMER ASSOC CANCER RESEARCH 71 (7) 2781 - 2792 0008-5472 2011/04 [Refereed]
   

  The expression of tumor suppressor Arf is tightly repressed during normal cell growth at a young age and is activated by oncogenic insults, and during aging, results in p53 activation and cell-cycle arrest to prevent hyperproliferation. The mechanisms of both transcriptional repression and activation of Arf are not understood. We show that p53 binds to and represses Arf expression and that this repression requires the function of both histone deacetylases (HDAC) and polycomb group (PcG) proteins. Inactivation of p53 leads to increased Arf transcription in both mouse embryonic fibroblasts (MEF) cultured in vitro and in tissues and organs of p53 null mice. Activation of endogenous p53 enhances Arf repression, and reintroduction of p53 back into p53 null MEFs restores Arf repression. Both DNA binding and transactivation activities of p53 are required for Arf repression. We show that p53 is required for both HDAC and PcG to repress Arf expression. Bindings of both HDAC and PcG to Arf are disrupted by inactivation of p53 and can be restored in p53 null MEFs by the reintroduction of wildtype, but not mutant, p53. These results indicate that p53 recruits both HDAC and PcG to Arf locus to repress its expression, and this repression constitutes a second feedback loop in p53 regulation. Cancer Res; 71(7); 2781-92. (C)2011 AACR.
• NFAT5 regulates transcription of the mouse telomerase reverse transcriptase gene

  Tsukasa Fujiki; Miyako Udono; Yojiro Kotake; Makiko Yamashita; Sanetaka Shirahata; Yoshinori Katakura

  EXPERIMENTAL CELL RESEARCH ELSEVIER INC 316 (20) 3342 - 3350 0014-4827 2010/12 [Refereed]
   

  We aimed to clarify the transcription-regulation mechanisms of the mouse telomerase reverse transcriptase gene (mTERT). First, we searched for the promoter region required for transcriptional activation of mTERT and identified an enhancer cis-element (named mTERT-EE) located between -200 and -179 bp of the mouse TERT gene (mTERT). EMSA results suggested that nuclear factor of activated T cells (NFAT) member proteins bind to mTERT-EE. We then identified NFAT5 as the factor binding to mTERT-EE and found that it activates the transcription of the mTERT core promoter. The results that siRNA directed against NFAT5 significantly reduced mTERT expression and mTERT core promoter activity and that the expressions of NFAT5 and mTERT were well correlated in various mouse tissues except liver suggest that NFAT5 dominantly and directly regulates mTERT expression. To clarify their functionality further, we investigated the effect of hypertonic stress, a known stimulus affecting the expression and transcriptional activity of NFAT5, on mTERT expression. The result indicated that hypertonic stress activates mTERT transcription via the activation and recruitment of NFAT5 to the mTERT promoter. These results provide useful information about the transcription-regulation mechanisms of mTERT. (C) 2010 Elsevier Inc. All rights reserved.
• GSK3 regulates the expressions of human and mouse c-Myb via different mechanisms

  Kyoko Kitagawa; Yojiro Kotake; Yoshihiro Hiramatsu; Ning Liu; Sayuri Suzuki; Satoki Nakamura; Akira Kikuchi; Masatoshi Kitagawa

  CELL DIVISION BIOMED CENTRAL LTD 5 (27) 1747-1028 2010/11 [Refereed]
   

  Background: c-Myb is expressed at high levels in immature progenitors of all the hematopoietic lineages. It is associated with the regulation of proliferation, differentiation and survival of erythroid, myeloid and lymphoid cells, but decreases during the terminal differentiation to mature blood cells. The cellular level of c-Myb is controlled by not only transcriptional regulation but also ubiquitin-dependent proteolysis. We recently reported that mouse c-Myb protein is controlled by ubiquitin-dependent degradation by SCF-Fbw7 E3 ligase via glycogen synthase kinase 3 (GSK3)-mediated phosphorylation of Thr-572 in a Cdc4 phosphodegron (CPD)-dependent manner. However, this critical threonine residue is not conserved in human c-Myb. In this study, we investigated whether GSK3 is involved in the regulatory mechanism for human c-Myb expression. Results: Human c-Myb was degraded by ubiquitin-dependent degradation via SCF-Fbw7. Human Fbw7 ubiquitylated not only human c-Myb but also mouse c-Myb, whereas mouse Fbw7 ubiquitylated mouse c-Myb but not human c-Myb. Human Fbw7 mutants with mutations of arginine residues important for recognition of the CPD still ubiquitylated human c-Myb. These data strongly suggest that human Fbw7 ubiquitylates human c-Myb in a CPD-independent manner. Mutations of the putative GSK3 phosphorylation sites in human c-Myb did not affect the Fbw7-dependent ubiquitylation of human c-Myb. Neither chemical inhibitors nor a siRNA for GSK3 beta affected the stability of human c-Myb. However, depletion of GSK3 beta upregulated the transcription of human c-Myb, resulting in transcriptional suppression of gamma-globin, one of the c-Myb target genes. Conclusions: The present observations suggest that human Fbw7 ubiquitylates human c-Myb in a CPD-independent manner, whereas mouse Fbw7 ubiquitylates human c-Myb in a CPD-dependent manner. Moreover, GSK3 negatively regulates the transcriptional expression of human c-Myb but does not promote Fbw7-dependent degradation of human c-Myb protein. Inactivation of GSK3 as well as mutations of Fbw7 may be causes of the enhanced c-Myb expression observed in leukemia cells. We conclude that expression levels of human and mouse c-Myb are regulated via different mechanisms.
• 癌化シグナルによるCDKインヒビターp16の転写活性化機構の解明

  神武洋二郎

  東京生化学研究会助成研究報告集 24 96 - 100 2010/06
• Adenovirus E1A Inhibits SCFFbw7 Ubiquitin Ligase

  Tomoyasu Isobe; Takayuki Hattori; Kyoko Kitagawa; Chiharu Uchida; Yojiro Kotake; Isao Kosugi; Toshiaki Oda; Masatoshi Kitagawa

  JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 284 (41) 27766 - 27779 0021-9258 2009/10 [Refereed]
   

  The SCFFbw7 ubiquitin ligase complex plays important roles in cell growth, survival, and differentiation via the ubiquitin-proteasome-mediated regulation of protein stability. Fbw7 (also known as Fbxw7, Sel-10, hCdc4, or hAgo), a substrate recognition subunit of SCFFbw7 ubiquitin ligase, facilitates the degradation of several proto-oncogene products by the proteasome. Given that mutations in Fbw7 are found in various types of human cancers, Fbw7 is considered to be a potent tumor suppressor. In the present study, we show that E1A, an oncogene product derived from adenovirus, interferes with the activity of the SCFFbw7 ubiquitin ligase. E1A interacted with SCFFbw7 and attenuated the ubiquitylation of its target proteins in vivo. Furthermore, using in vitro purified SCFFbw7 component proteins, we found that E1A directly bound to Roc1/Rbx1 and CUL1 and that E1A inhibited the ubiquitin ligase activity of the Roc1/Rbx1-CUL1 complex but not that of another RING-type ubiquitin ligase, Mdm2. Ectopically expressed E1A interacted with cellular endogenous Roc1/Rbx1 and CUL1 and decelerated the degradation of several protooncogene products that were degraded by SCFFbw7 ubiquitin ligase. Moreover, after wild-type adenovirus infection, adenovirus-derived E1A interacted with endogenous Roc1/Rbx1 and decelerated degradation of the endogenous target protein of SCFFbw7. These observations demonstrated that E1A perturbs protein turnover regulated by SCFFbw7 through the inhibition of SCFFbw7 ubiquitin ligase. Our findings may help to explain the mechanism whereby adenovirus infection induces unregulated proliferation.
• Ubiquitin-mediated control of oncogene and tumor suppressor gene products

  Kyoko Kitagawa; Yojiro Kotake; Masatoshi Kitagawa

  CANCER SCIENCE WILEY-BLACKWELL PUBLISHING, INC 100 (8) 1374 - 1381 1347-9032 2009/08 [Refereed]
   

  Cellular levels of products from both oncogenes and tumor suppressor genes in normal cells need to be critically regulated to avoid malignant transformation. These products are often controlled by the ubiquitin proteasome pathway, the specific degradation mechanism in the cell. E3 ubiquitin ligases polyubiquitylate their specific substrates by collaborating with E1 and E2, and then the modified substrates are degraded in the proteasome. Mdm2 targets p53 and retinoblastoma protein, two major tumor suppressor gene products, for ubiquitin-dependent degradation. SCF(Skp2) targets other tumor suppressor gene products and CDK inhibitors such as p130, Tob1, p27(Kip1), p57(Kip2), and p21(Cip1). Therefore, both E3 ligases act like oncogene products. In contrast, degradation of several oncogene products, such as Cyclin E, Notch, c-Myc, c-Jun, and c-Myb, are mediated by SCF(Fbw7). Fbw7 is often deleted or mutated in human cancers and acts like a tumor suppressor. As well as growth factor receptors and signal transduction regulators, DNA repair-related proteins are also regulated via the ubiquitin-proteasome pathway mediated by their specific E3 ligases. The stabilization of oncogene products and enhanced degradation of tumor suppressor gene products or DNA repair proteins might be associated with carcinogenesis and malignant progression, due to defects or the abnormal expression of their E3 ligases. (Cancer Sci 2009).
• High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers

  Mai Shimada; Kyoko Kitagawa; Yoh Dobashi; Tomoyasu Isobe; Takayuki Hattori; Chiharu Uchida; Kenji Abe; Yojiro Kotake; Toshiaki Oda; Hiroyuki Suzuki; Kenji Hashimoto; Masatoshi Kitagawa

  CANCER SCIENCE WILEY-BLACKWELL 100 (5) 866 - 872 1349-7006 2009/05 [Refereed]
   

  Downregulation of the cyclin-dependent kinase inhibitory protein p27 is frequently observed in various cancers due to enhancement of its degradation. We recently reported that p53-inducible protein with RING-H2 domain (Pirh2) is a novel ubiquitin ligase for p27, required for the ubiquitylation and consequent degradation of p27 protein. However, there is no reports about the involvement of Pirh2 in both p27 downregulation and pathogenesis in human cancers. In the present study, we investigated them using cultured cell lines and surgical specimens derived from human head and neck squamous cell carcinoma (HNSCC). Depletion of Pirh2 by short interfering RNA induced accumulation of p27 and inhibited the growth of cultured HNSCC cells. By immunohistochemical analysis in 57 cases of HNSCC specimens, higher levels of Pirh2 expression (labeling index >= 60%) were found in 61.4% of HNSCC in comparison with 0% of normal mucosa. In addition, 83.3% of HNSCC with lower p27 expression (labeling index < 20%) displayed high Pirh2 levels. Therefore, Pirh2 expression was inversely correlated with p27 expression. Finally, Pirh2 expression was well correlated with poor prognosis. These findings suggest that Pirh2 overexpression may have an important role in the development and maintenance of HNSCC at least partially through p27 degradation, and that Pirh2 may be a potential molecular target for human HNSCC. (Cancer Sci 2009; 100: 866-872).
• DDB1-CUL4 and MLL1 Mediate Oncogene-Induced p16(INK4a) Activation

  Yojiro Kotake; Yaxue Zeng; Yue Xiong

  CANCER RESEARCH AMER ASSOC CANCER RESEARCH 69 (5) 1809 - 1814 0008-5472 2009/03 [Refereed]
   

  The induction of cellular senescence by oncogenic signals acts as a barrier to cellular transformation and is attained, in part, by the elevation of the p16(INK4a) tumor suppressor gene. p16 expression is repressed epigenctically by Polycomb, but how p16 is induced is not known. We report here that the p16 locus is H3K4-methylated in highly expressing cells. H3K4 methyltransferase MLL1 directly binds to and is required, along with its core component RbBP5, for the induction of p16 by oncogenic Ras. We further show that damaged DNA binding protein DDB1 and CUL4, which assemble distinct E3 ubiquitin ligases by recruiting various WD40 proteins, act upstream of MLL1-mediated H3K4 methylation. We showed that CUL4A directly binds to p16 and that silencing DDB1 blocks Ras-induced p16 activation. Ras expression dissociates BM11 from the p16 locus, whereas both CUL4 and MLL1 bind to the p16 locus similarly in both normal and oncogenic stimulated cells. These results suggest that DDB1-CUL4 and MLL1 complexes constitute a novel pathway that mediates p16 activation during oncogenic checkpoint response and is repressed by the polycomb repression complexes during normal growth of young cells. [Cancer Res 2009;69(5):1809-14]
• Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development

  Chad M. McCall; Paula L. Miliani de Marval; Paul D. Chastain; Sarah C. Jackson; Yizhou J. He; Yojiro Kotake; Jeanette Gowen Cook; Yue Xiong

  MOLECULAR AND CELLULAR BIOLOGY AMER SOC MICROBIOLOGY 28 (18) 5621 - 5633 0270-7306 2008/09 [Refereed]
   

  Damaged DNA binding protein 1, DDB1, bridges an estimated 90 or more WD40 repeats (DDB1-binding WD40, or DWD proteins) to the CUL4-ROC1 catalytic core to constitute a potentially large number of E3 ligase complexes. Among these DWD proteins is the human immunodeficiency virus type 1 (HIV-1) Vpr-binding protein VprBP, whose cellular function has yet to be characterized but has recently been found to mediate Vpr-induced G(2) cell cycle arrest. We demonstrate here that VprBP binds stoichiometrically with DDB1 through its WD40 domain and through DDB1 to CUL4A, subunits of the COP9/signalsome, and DDA1. The steady-state level of VprBP remains constant during interphase and decreases during mitosis. VprBP binds to chromatin in a DDB1-independent and cell cycle-dependent manner, increasing from early S through G(2) before decreasing to undetectable levels in mitotic and G(1) cells. Silencing VprBP reduced the rate of DNA replication, blocked cells from progressing through the S phase, and inhibited proliferation. VprBP ablation in mice results in early embryonic lethality. Conditional deletion of the VprBP gene in mouse embryonic fibroblasts results in severely defective progression through S phase and subsequent apoptosis. Our studies identify a previously unknown function of VprBP in S-phase progression and suggest the possibility that HIV-1 Vpr may divert an ongoing chromosomal replication activity to facilitate viral replication.
• pRB family proteins are required for H3K27 trimethylation and polycomb repression complexes binding to and silencing p16(INK4a) tumor suppressor gene

  Yojiro Kotake; Ru Cao; Patrick Viatour; Julien Sage; Yi Zhang; Yue Xiong

  GENES & DEVELOPMENT COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT 21 (1) 49 - 54 0890-9369 2007/01 [Refereed]
   

  Genetic studies have demonstrated that Bmi1 promotes cell proliferation and stem cell self-renewal with a correlative decrease of p16(INK4a) expression. Here, we demonstrate that Polycomb genes EZH2 and BMI1 repress p16 expression in human and mouse primary cells, but not in cells deficient for pRB protein function. The p16 locus is H3K27-methylated and bound by BMI1, RING2, and SUZ12. Inactivation of pRB family proteins abolishes H3K27 methylation and disrupts BMI1, RING2, and SUZ12 binding to the p16 locus. These results suggest a model in which pRB proteins recruit PRC2 to trimethylate p16, priming the BMI1-containing PRC1L ubiquitin ligase complex to silence p16.
• No exit strategy? No problem: APC inhibits beta-catenin inside the nucleus

  Y Xiong; Y Kotake

  GENES & DEVELOPMENT COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT 20 (6) 637 - 642 0890-9369 2006/03 [Refereed]
  
• Role of serine 10 phosphorylation in p27 stabilization revealed by analysis of p27 knock-in mice harboring a serine 10 mutation

  Y Kotake; K Nakayama; N Ishida; KI Nakayama

  JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 280 (2) 1095 - 1102 0021-9258 2005/01 [Refereed]
   

  The inhibition of cyclin-dependent kinase activity by p27 contributes to regulation of cell cycle progression. Serine 10 is the major phosphorylation site of p27, and its phosphorylation has been shown to affect the stability and nuclear export of p27 at the G(0)-G(1) transition in transfected cultured cells. To investigate the physiological relevance of p27 phosphorylation on Ser(10), we generated p27 "knock-in" mice that harbor an S10A mutation in this protein. Mice homozygous for the mutation (p27(S10A/S10A) mice) were normal in body size, but the abundance of p27 was decreased in many organs, including brain, thymus, spleen, and testis. The stability of p27 in G(0) phase was markedly reduced in lymphocytes of p27(S10A/S10A) mice compared with that in wild-type cells, whereas p27 stability in S phase was similar in cells of the two genotypes. The degradation of p27 in cells of the mutant mice at G(0) phase was prevented by a proteasome inhibitor. These data indicate that the physiological role of p27 phosphorylation on Ser(10) is to stabilize the protein in G(0) phase. Unexpectedly, the nuclear export of p27 at the G(0)-G(1) transition occurred normally in p27(S10A/S10A) mouse embryonic fibroblasts, indicating that phosphorylation of Ser(10) is dispensable for this process.
• CDKインヒビターp27Kip1のタンパク質分解による制御機構

  神武 洋二郎; 中山 敬一

  遺伝子医学 7 (24) 79 - 85 2003/06
• Transcriptional regulation mechanisms of telomerase reverse transcriptase gene responsible for ubiquitous expression of telomerase in mouse

  T Fujiki; Y Katakura; T Miura; Y Kotake; K Yoshizaki; S Shirahata

  ANIMAL CELL TECHNOLOGY: BASIC & APPLIED ASPECTS, VOL 13 SPRINGER 13 329 - 333 2003 [Refereed]
   

  Telomerase is known to maintain the telomere by avoiding the shortening of the telomere which normally occurs during end replication, thus granting immortality to cancer cells and stem cells. Telomerase activity is thought to be regulated mainly at the transcriptional level. Furthermore, the telomerase regulation mechanism is reported to be markedly different between human and mouse. Particularly, telomerase has been shown not to be expressed in normal human tissues, but abundant expression has been shown to be expressed in all mouse tissues except in brain and muscle tissue. By using various deletion mutants of mouse telomerase reverse transcriptase (mTERT) promoter in promoter assay, we obtained result that -200 to -178 by from the translational start site confers a strong transcriptional activity in mTERT promoter, where NF-AT and v-Myb are expected to bind. Although v-Myb could not activate the promoter, NF-AT member proteins, especially NF-AT5 could activate the 5 tandem repeat of -200 to -178 fused to luciferase gene (mTERT-EE). Furthermore, dominant negative mutants of NF-AT5 repressed promoter activity of mTERT-EE. These results demonstrate that NF-AT5 activates the mTERT promoter activity via binding to -200 to 178 region, which might confers the ubiquitous expression of mTERT.

Books etc

• ノンコーディングRNAテキストブック

  神武洋二郎 (Contributor第2章6節)羊土社 実験医学増刊 2015/12
• 遺伝子治療・診断の最先端技術と新しい医薬品・診断薬の開発

  藤井政幸; 高科あゆみ; 神武洋二郎; 森田資隆; 山田康枝 (Contributor第6章第3節)技術情報協会 2014/05
• 長鎖ノンコーディングRNAと細胞老化.

  神武洋二郎; 北川雅敏 (Contributor)秀潤社 細胞工学 第30巻7号 pp.729-733 2011/07
• 長鎖ncRNAによるクロマチン修飾因子のリクルートメント機構.

  神武洋二郎; 北川雅敏 (Joint work)羊土社 実験医学 第29巻11号 pp.1716-1721 2011/07

Conference Activities & Talks

• The cell cycle regulation by long noncoding RNAs.  [Not invited]

  Yojiro Kotake; Yoshinobu Tanigawa; Ryoka Tarumi; Takahiro Wakasaki

  The 30th FAOBMB & 8th BMB Conference  2023/11
• 長鎖ノンコーディングRNA,OIP5-AS1による癌細胞増殖制御機構の解明

  谷川由信; 若崎高裕; 神武洋二郎

  第60回化学関連支部合同九州大会  2023/07
• レスベラトロール誘導体による癌細胞増殖抑制効果の検証と作用機序の解明

  樽見 涼花; 谷川由信; 神武 洋二郎

  第60回化学関連支部合同九州大会  2023/07
• 長鎖非コードRNA OIP5-AS1とANROCによる細胞周期制御.

  神武洋二郎; 谷川由信; 樽見涼花; 若崎高裕

  日本薬学会第143年会  2023/03
• 長鎖ノンコーディングRNA, OIP5-AS1による頭頸部癌及び大腸癌の増殖制御.

  谷川由信; 若崎高裕; 神武洋二郎

  日本農芸化学会2023年度大会  2023/03
• 癌遺伝子YB1による細胞周期制御.

  神武洋二郎; 若崎高裕

  日本農芸化学会2023年度大会  2023/03
• 長鎖ノンコーディングRNAによる細胞周期の制御.  [Invited]

  神武洋二郎

  東京農業大学大学院生命科学研究科セミナー  2022/06
• 長鎖ノンコーディングRNA, ANROCとOIP5-AS1による細胞増殖制御機構

  神武洋二郎, 岡田凌太朗

  日本農芸化学会2022年度大会  2022/03
• フェルラ酸が付加したレスベラトロール誘導体による癌細胞三次元増殖阻害効果の検証と作用機構の解明

  岡田凌太朗; 松川泰治; 土井聡; 大貫宏一郎; 神武 洋二郎

  第58回化学関連支部合同九州大会  2021/07
• INK4遺伝子座から転写される2つの長鎖ノンコーディングRNAの機能解析

  神武洋二郎; 松永夏実; 岡田凌太朗

  日本農芸化学会2021年度大会  2021/03
• 長鎖ノンコーディングRNAによる頭頸部扁平上皮癌増殖制御

  松永夏実; 若崎高裕; 安松隆治; 岡田凌太朗; 神武洋二郎

  第43回日本分子生物学会年会, オンライン  2020/12
• 新規レスベラトロール誘導体は癌抑制遺伝子p15を誘導し、大腸癌及び乳癌細胞の三次元増殖を抑制する

  岡田凌太朗; 澤田悠賀; 松川泰治; 土井聡; 角田俊之; 松永夏実; 大貫宏一郎; 白澤専二; 神武洋二郎

  第43回日本分子生物学会年会, オンライン  2020/12
• 長鎖非コードRNA OIP5-AS1 による細胞周期制御機構

  松永夏実; 岡田凌太朗; 神武洋二郎

  2020年度日本フードファクター学会・日本農芸化学会西日本支部合同大会  2020/11
• フェルラ酸が付加したレスベラトロール誘導体による抗癌作用の検証と作用機序の解明.

  岡田凌太朗; 松川泰治; 土井聡; 松永夏実; 大貫宏一郎; 神武洋二郎

  2020年度日本フードファクター学会・日本農芸化学会西日本支部合同大会  2020/11
• がん化シグナルによって発現量が減少する長鎖ノンコーディングRNAの機能解明  [Not invited]

  松永夏実; 神武洋二郎

  第42回日本分子生物学会  2019/12
• 長鎖ノンコーディングRNAによる頭頸部癌細胞の増殖制御機構の解明  [Not invited]

  松永夏実; 神武洋二郎

  2019年度日本農芸化学会西日本・中四国支部合同大会  2019/11
• Chemical Modification of siRNA Eliminating Off-target Effect of the Sense Strand

  Yasuo Shiohama; Takashi Fujita; Shuichi Miyata; Yojiro Kotake; Masayuki Fujii

  The 46th International Symposium of Nucleic Acid Chemistry  2019/10
• 頭頸部癌細胞におけるANRILとOIP5-AS1の機能解明  [Not invited]

  松永夏実; 神武洋二郎

  近畿大学大学院サイエンスネットワーク2019  2019/10
• The regulation of INK4 locus by long non-coding RNAs  [Not invited]

  Yojiro Kotake; Natsumi Matsunaga; Yuuga Sawata; Nagisa Arikawa

  ESMO Congress 2019  2019/09
• INK4遺伝子座に存在する長鎖ノンコーディングRNAの機能解明  [Not invited]

  鶴田健志; 松永夏実; 神武洋二郎

  第56回化学関連支部合同九州大会  2019/07
• 長鎖ノンコーディングRNA ANRILは、 頭頸部癌細胞の増殖を促進する機能を持つ  [Not invited]

  松永夏実; 神武 洋二郎

  第56回化学関連支部合同九州大会  2019/07
• 長鎖ノンコーディングRNA OIP5-AS1はガン細胞増殖を制御する  [Not invited]

  永易康生; 松永夏実; 神武洋二郎

  第56回化学関連支部合同九州大会  2019/07
• The functional analysis of long noncoding RNAs affected by oncogenic Ras signaling  [Not invited]

  Yojiro Kotake; Natsumi Matsunaga; Yuuga Sawata; Nagisa Arikawa

  The FEBS Congress 2019  2019/07
• 長鎖ノンコーディングRNAによる細胞周期制御機構  [Invited]

  神武洋二郎

  福岡大学基盤研究機関先端分子医学研究所セミナー  2019/06
• 転写因子YB-1によるG2/M期制御機構の解明  [Not invited]

  有川和沙; 澤田悠賀; 神武洋二郎

  第41回日本分子生物学会  2018/11
• 大腸癌細胞三次元増殖を抑制する新規レスベラトロール誘導体の探索とその作用機構の解明  [Not invited]

  澤田悠賀; 松川泰治; 土井聡; 角田俊之; 有川和沙; 大貫宏一郎; 白澤専二; 神武洋二郎

  第41回日本分子生物学会  2018/11
• 新規レスベラトロール誘導体による大腸癌細胞三次元増殖抑制機構の解明  [Not invited]

  澤田悠賀; 松川泰治; 土井聡; 有川和沙; 大貫宏一郎; 神武洋二郎

  近畿大学サイエンスネットワーク2018・第8回院生サミッ  2018/09
• 転写因子YB-1は細胞周期のG1及びG2/M期制御に関与する  [Not invited]

  有川和沙; 澤田悠賀; 神武洋二郎

  近畿大学サイエンスネットワーク2018・第8回院生サミッ  2018/09
• Oncogenic Ras signalling affects the expression of multiple lncRNAs including a functional lncRNA, ANRIL.  [Not invited]

  Kotake Y; Arikawa N; Sawata Y; Matsunaga N

  EMBO Workshop Cellular signalling and cancer therapy  2018/09
• Long noncoding RNA, ANRIL positively regulates cell proliferation in a p15/p16-dependent and –independent manners  [Not invited]

  yojiro Kotake

  25TH BIENNIAL CONGRESS OF THE EUROPEAN ASSOCIATION FOR CANCER RESEARCH  2018/07
• 新規レスベラトロール誘導体によるがん細胞三次元増殖抑制機構の解明  [Not invited]

  澤田悠賀; 松川泰治; 土井聡; 有川和沙; 大貫宏一郎; 神武洋二郎

  第55回化学関連支部合同九州大会  2018/06
• 転写因子YB-1による細胞周期制御機構の解明  [Not invited]

  有川和沙; 澤田悠賀; 神武洋二郎

  第55回化学関連支部合同九州大会  2018/06
• 長鎖ノンコーディングRNA ANRILはガン細胞増殖を促進する機能を持つ  [Not invited]

  松永夏実; 有川和沙; 澤田悠賀; 神武洋二郎

  第55回化学関連支部合同九州大会  2018/06
• 新規レスベラトロール誘導体は大腸癌細胞三次元増殖を抑制する  [Not invited]

  澤田 悠賀; 松川 泰治; 土井 聡; 角田 俊之; 岡本 春奈; 苗村 円佳; 田原 圭一郎; 有川 和沙; 松岡 耕平; 原田 正樹; 大貫 宏一郎; 白澤 専二; 神武 洋二郎

  第40回日本分子生物学会年会  2017/12
• 転写因子YB-1による細胞老化抑制機構  [Not invited]

  有川和沙; 田原圭一郎; 向井勝馬; 苗村円佳; 澤田悠賀; 神武洋二郎

  第40回日本分子生物学会年会  2017/12
• 大腸癌細胞増殖を抑制するレスベラトロール誘導体の探索  [Not invited]

  澤田悠賀; 松川泰治; 土井聡; 岡本春奈; 苗村円佳; 田原圭一郎; 有川和沙; 松岡耕平; 原田正樹; 大貫宏一郎; 神武洋二郎

  2017近畿大学サイエンスネットワーク・第7回院生サミット  2017/09
• ガン細胞における転写因子YB-1の機能解明  [Not invited]

  有川和沙; 田原圭一郎; 向井勝馬; 苗村円佳; 澤田悠賀; 神武洋二郎

  2017近畿大学サイエンスネットワーク・第7回院生サミット  2017/09
• ガン化シグナルによって発現変動する長鎖非コードRNAの探索と機能解析  [Not invited]

  苗村円佳; 有川和沙; 澤田悠賀; 田原圭一郎; 神武洋二郎

  2017近畿大学サイエンスネットワーク・第7回院生サミット  2017/09
• Long noncoding RNA, ANRIL positively regulates cell proliferation in a p15/p16-dependent and –independent manners  [Not invited]

  25TH BIENNIAL CONGRESS OF THE EUROPEAN ASSOCIATION FOR CANCER RESEARCH  2017/07
• YB-1によるガン抑制遺伝子p16転写抑制機構の解明  [Not invited]

  田原圭一郎; 有川和沙; 苗村円佳; 澤田悠賀; 神武洋二郎

  第54回化学関連支部合同九州大会  2017/07
• 転写因子YB-1によるガン細胞増殖制御機構の解明  [Not invited]

  有川和沙; 田原圭一郎; 苗村円佳; 澤田悠賀; 神武洋二郎

  第54回化学関連支部合同九州大会  2017/07
• 新規レスベラトロール誘導体による大腸癌細胞増殖抑制機構  [Not invited]

  澤田悠賀; 松川泰治; 土井聡; 岡本春奈; 苗村円佳; 田原圭一郎; 有川和沙; 大貫宏一郎; 神武洋二郎

  第54回化学関連支部合同九州大会  2017/07
• 細胞老化、アポトーシスを制御する長鎖ノンコーディングRNA  [Invited]

  神武洋二郎

  第69回日本細胞生物学会大会  2017/06
• Long Noncoding RNA, ANRIL Regulates Cell Proliferation Via Repressing INK4 Locus.  [Not invited]

  Kotake Y; Naemura M; Tahara K; Arikawa N; Sawata Y

  EMBO conference-Chromatin and Epigenetics  2017/05
• 細胞周期制御に関与する長鎖ノンコーディングRNAの機能解析  [Not invited]

  神武洋二郎; 苗村円佳; 井上恭敏; 岡本春奈; 田原圭一郎

  日本農芸化学会2017年度大会  2017/03
• A novel long noncoding RNA positively regulates cancer cell proliferation  [Not invited]

  J.I.S.R.I.2016  2016/12
• 化学修飾siRNAのRNA干渉効果への影響  [Not invited]

  新貝恭広; 苗村円佳; 神武洋二郎; 山吉麻子; 有吉順平; Alesya A. F; Dmitry A. S; Vyacheslav V. F; 藤井政幸

  日本核酸医薬学会第二回年会  2016/11
• Roles of long noncoding RNAs, ANRIL and PANDA, in RB and p53 pathways  [Invited]

  yojiro Kotake

  The 2nd International Symposium of Chemistry and Biology of RNA Interference  2016/09
• 新規長鎖ノンコーディングRNAの作用機構と細胞内機能の解明  [Not invited]

  井上恭敏; 苗村円佳; 濱崎彩花; 中川飛鳥; 神武洋二郎

  第15回近畿大学環境科学研究会  2016/08
• Long Noncoding RNA, ANRIL Regulates the Proliferation of Non-Small Cell Lung and Colorectal Cancer Cells  [Not invited]

  Madoka Naemura; Yasutoshi Inoue; Haruna Okamoto; Keiichiro Tahara; Yojiro Kotake

  12th International Congress of Cell Biology  2016/07
• siRNAの構造と遺伝子サイレンシング効果への影響  [Not invited]

  新貝恭広; 柏原慎一; 峰松剛; 藤井政幸; 苗村 円佳; 神武洋二郎

  第53回化学関連支部合同九州大会  2016/07
• 新規両親媒性ペプチドによるsiRNAの無毒生細胞導入と遺伝子サイレンシング  [Not invited]

  柏原慎一; 新貝恭広; 藤井啓史; 藤井政幸; 苗村まどか; 神武洋二郎

  第53回化学関連支部合同九州大会  2016/07
• レスベラトロール及びその誘導体は大腸癌細胞三次元増殖を抑制する  [Not invited]

  岡本春奈; 松川泰治; 苗村円佳; 井上恭敏; 田原圭一郎; 大貫宏一郎; 神武洋二郎

  第53回化学関連支部合同九州大会  2016/07
• 転写因子YB-1による細胞老化抑制機構  [Not invited]

  田原圭一郎; 苗村円佳; 井上恭敏; 岡本春奈; 神武洋二郎

  第53回化学関連支部合同九州大会  2016/07
• Two long non-coding RNAs that are involved in the transcriptional repression of INK4 locus  [Not invited]

  Yasutoshi Inoue; Madoka Naemura; Haruna Okamoto; Keiichiro Tahara; Yojiro Kotake

  第53回化学関連支部合同九州大会  2016/07
• Long noncoding RNA ANRIL represses the expression of INK4 locus  [Not invited]

  Madoka Naemura; Yasutoshi Inoue; Haruna Okamoto; Keiichiro Tahara; Yojiro Kotake

  第53回化学関連支部合同九州大会  2016/07
• がん化シグナルよって発現誘導される新規長鎖ノンコーディングRNAの機能解明  [Not invited]

  井上恭敏; 苗村円佳; 濱崎彩花; 中川飛鳥; 岡本春奈; 田原圭一郎; 神武洋二郎

  第68回日本細胞生物学会大会  2016/06
• 長鎖ノンコーディングRNA, ANRILによる細胞増殖促進機構の解明  [Not invited]

  苗村 円佳; 角田 俊之; 井上 恭敏; 岡本 春奈; 田原 圭一郎; 白澤 専二; 神武 洋二郎

  第68回日本細胞生物学会大会  2016/06
• 細胞老化における転写因子YB-1の機能解明  [Not invited]

  田原圭一郎; 苗村円佳; 井上恭敏; 岡本春奈; 北川雅敏; 神武洋二郎

  第68回日本細胞生物学会大会  2016/06
• INK4遺伝子座に存在する長鎖非コードRNA, ANRILの機能解析  [Not invited]

  苗村 円佳; 角田 俊之; 紫 千大; 井上 恭敏; 岡本 春奈; 白澤 専二; 神武 洋二郎

  第19回バイオ治療法研究会  2015/12
• カチオン性5’-末端を有するsiRNAの遺伝子サイレンシング効果  [Not invited]

  藤井 政幸; 大野 結有; 新貝 恭広; 藤井 啓史; 柏原 慎一; 苗村 円佳; 神武洋二郎; 山吉 麻子; 村上 章

  日本核酸医薬学会第1回年会  2015/11
• 5’-アミノTを有するsiRNAの遺伝子サイレンシング効果  [Not invited]

  新貝恭広; 藤井啓史; 柏原慎一; 苗村円佳; 神武洋二郎; 山吉麻子; 村上章; 藤井政幸

  日本核酸医薬学会第1回年会  2015/11
• ミスマッチまたはバルジ構造を有するmiRNA様siRNAの遺伝子サイレンシング効果  [Not invited]

  藤井 政幸; 新貝 恭広; 藤井 啓史; 柏原 慎一; 苗村 円佳; 神武洋二郎; 山吉 麻子; 村上 章

  日本核酸医薬学会第1回年会  2015/11
• LONG NONCODING RNA ANRIL PROMOTES PROLIFERATION OF CANCER CELLS  [Not invited]

  Madoka Naemura; Chihiro Murasaki; Yasutoshi Inoue; Haruna Okamoto; Yojiro Kotake

  2015/11
• THE FUNCTIONAL ANALYSIS OF NOVEL LONG NON-CODING RNA INVOLVED IN CARCINOGENESIS  [Not invited]

  Yasutoshi Inoue; Madoka Naemura; Chihiro Murasaki; Haruna Okamoto; Yojiro Kotake

  Joint International Symposium on「Regional Revitalization and Innovation for Social Contribution」 and and「e-ASIA Functional Materials and Biomass Utilization 2015」  2015/11
• 長鎖ノンコーディングRNAによるRB/p53経路の制御機構  [Not invited]

  神武洋二郎; 苗村円佳; 紫千大; 井上恭敏; 岡本春奈

  ２０１５年度 日本農芸化学会中四国支部・西日本支部合同大会  2015/09
• 新規ハイブリッドペプチドによる siRNA の無毒性細胞内導入  [Not invited]

  柏原慎一; 新貝恭広; 藤井啓史; 大野結有; 赤池香菜実; 苗村円佳; 神武洋二郎; 藤井 政幸

  第9回バイオ関連化学シンポジウム  2015/09
• 5’-アミノTを有するsiRNAの遺伝子サイレンシング効果  [Not invited]

  大野結有; 赤池香菜実; 新貝恭広; 藤井啓史; 柏原慎一; 苗村円佳; 神武洋二郎; 山吉麻子; 村上章; 藤井政幸

  第9回バイオ関連化学シンポジウム  2015/09
• miRNA様siRNAの遺伝子サイレンシング効果  [Not invited]

  新貝恭広; 藤井啓史; 大野結有; 赤池香菜実; 柏原慎一; 苗村円佳; 神武洋二郎; 山吉麻子; 村上章; 藤井政幸

  第9回バイオ関連化学シンポジウム  2015/09
• がん細胞における長鎖ノンコーディングRNA, ANRILの機能とその作用機構の解明  [Not invited]

  苗村円佳; 紫千大; 井上恭敏; 岡本春奈; 神武洋二郎

  2015近畿大学サイエンスネットワーク・第5回院生サミット  2015/07
• ガン細胞増殖における新規長鎖ノンコーディングRNAの機能解析  [Not invited]

  井上恭敏; 苗村円佳; 紫千大; 岡本春奈; 神武洋二郎

  2015近畿大学サイエンスネットワーク・第5回院生サミット 和歌山市  2015/07
• レスベラトロール及びその誘導体は大腸癌細胞三次元増殖を抑制する  [Not invited]

  岡本春奈; 松川泰治; 苗村円佳; 井上恭敏; 田原圭一郎; 大貫宏一郎; 神武洋二郎

  第53回化学関連支部合同九州大会  2015/07
• 長鎖非コードRNA,ANRILはp15を抑制してがん細胞増殖を促進する  [Not invited]

  苗村円佳; 紫千大; 井上恭敏; 岡本春奈; 神武洋二郎

  第52回化学関連支部合同九州大会  2015/06
• レスベラトロールによる肺癌及び大腸癌細胞増殖抑制機構の解明  [Not invited]

  岡本春奈; 田村恵士; 松川泰治; 江頭央透; 苗村円佳; 紫千大; 井上恭敏; 大貫宏一郎; 神武洋二郎

  第52回化学関連支部合同九州大会  2015/06
• 長鎖ノンコーディングRNAによる骨肉腫細胞増殖制御機構の解明  [Not invited]

  紫千大; 苗村円佳; 井上恭敏; 岡本春奈; 神武洋二郎

  第52回化学関連支部合同九州大会  2015/06
• 化学修飾核酸の新規合成法  [Not invited]

  江見友裕; 髙松辰臣; 岡本大幹; 苗村円佳; 神武洋二郎; 藤井政幸

  第52回化学関連支部合同九州大会  2015/06
• 新規βシート型ハイブリッドペプチドによるsiRNAの無毒性細胞内導入  [Not invited]

  添田晃斉; 柏原慎一; 上野桃子; 末廣優一; 苗村円佳; 神武洋二郎; 藤井政幸

  第52回化学関連支部合同九州大会  2015/06
• ミスマッチ塩基対またはバルジ構造を有するmiRNA様siRNAの遺伝子サイレンシング効果  [Not invited]

  新貝恭広; 藤井 啓史; 苗村円佳; 神武洋二郎; 藤井政幸

  第52回化学関連支部合同九州大会  2015/06
• カチオン修飾siRNAによる遺伝子サイレンシング効果  [Not invited]

  大野結有; 赤池香菜実; 峰松剛; 苗村円佳; 神武洋二郎; 藤井政幸

  第52回化学関連支部合同九州大会  2015/06
• ガン化に関与する新規長鎖ノンコーディングRNAの探索と機能解析  [Not invited]

  井上恭敏; 苗村円佳; 中川飛鳥; 濱崎彩花; 紫千大; 岡本春奈; 神武洋二郎

  第52回化学関連支部合同九州大会  2015/06
• 癌細胞増殖における長鎖非コードRNA,ANRILの機能解明  [Not invited]

  苗村円佳; 紫千大; 神武洋二郎

  日本農芸化学会2015年度大会  2015/03
• カチオン修飾siRNAによる遺伝子サイレンシング効果  [Not invited]

  藤井政幸; 高科あゆみ; 苗村まどか; 神武洋二郎; 山吉麻子; 有吉純平; 村上章

  日本化学会第95春季年会  2015/03
• がん抑制遺伝子p15/p16を制御する長鎖非コードRNA, ANRILの機能解析  [Not invited]

  神武洋二郎; 苗村円佳; 紫千大

  第18回バイオ治療法研究会  2014/12
• Efficient Transfection of siRNA by designed peptides  [Not invited]

  Hikari Kayano; Ayumi Takashina; Madoka Naemura; Yojiro Kotake; Yasutaka Morita; Masayuki Fujii

  The 41st International Symposium on Nucleic Acids Chemistry  2014/11
• Regulation of RB and p53 pathways by long noncoding RNAs  [Invited]

  The 1st International Symposium of Chemistry and Biology of RNA Interference  2014/11
• siRNA-ペプチド複合体の細胞内導入と遺伝子サイレンシング効果  [Not invited]

  萱野光; 苗村円佳; 高科あゆみ; 神武洋二郎; 森田資隆; 藤井政幸

  第４回CSJ化学フェスタ 2014  2014/10
• YB-1 binds to and activates cyclinD1 transcriptional activities in Non-Small-Cell lung cancer  [Not invited]

  原田雅教; 神武洋二郎; 北川恭子; 丹伊田浩行; 椙村春彦; 北川雅敏

  第73回日本癌学会学術総会  2014/09
• 長鎖非コードRNA, ANRILによるがん細胞増殖制御機構の解明  [Not invited]

  苗村円佳; 紫千大; 神武洋二郎

  2014/09
• 癌細胞における長鎖ノンコーディングRNA, ANRILの機能解析  [Not invited]

  苗村円佳; 神武洋二郎

  第51回化学関連支部合同九州大会, 北九州市  2014/06
• 長鎖ノンコーディングRNAによる細胞死制御  [Not invited]

  紫千大; 苗村円佳; 神武洋二郎

  第51回化学関連支部合同九州大会, 北九州市  2014/06
• 高分子非コードRNA,ANRILの作用機序と細胞機能の解明  [Not invited]

  苗村円佳; 神武洋二郎

  日本農芸化学会2014年度大会  2014/03
• 細胞はなぜ老いるのか？  [Not invited]

  神武洋二郎

  第28回福岡県高等学校総合文化祭 自然科学部門 福岡県大会  2013/12
• The regulation of RB/p53 pathway by long noncoding RNAs  [Not invited]

  神武 洋二郎; 北川雅敏

  第36回日本分子生物学会年会  2013/12
• Elucidation of the action mechanism of long non-coding RNA, ANRIL which regulates cell proliferation  [Not invited]

  神武 洋二郎; 苗村円佳; 北川雅敏

  第36回日本分子生物学会年会  2013/12
• 非小細胞肺癌においてYB-1はcyclinD1の転写を亢進させる  [Not invited]

  神武 洋二郎; 原田雅教; 大畑樹也; アルディヤンティ アストリッド; 北川恭子; 丹伊田浩之; 椙村春彦; 須 隆文; 北川 雅敏

  第36回日本分子生物学会年会  2013/12
• 非小細胞肺癌においてYB-1はcyclinD1の転写を亢進させる  [Not invited]

  原田雅教; 神武洋二郎; 大畑樹也; アルディヤンティ アストリッド; 北川恭子; 丹伊田浩之; 椙村春彦; 須 隆文; 北川 雅敏

  第36回日本分子生物学会年会  2013/12
• 長鎖非コードRNA,ANRILによる細胞老化制御機構の解明  [Not invited]

  神武 洋二郎; 苗村円佳

  2013近畿大学サイエンスネットワーク・院生サミット  2013/11  2013近畿大学サイエンスネットワーク・院生サミット
  
• 癌化シグナルによる細胞内環境変化に伴って発現変動する長鎖ノンコーディングRNAの探索と機能解析  [Not invited]

  神武 洋二郎; 苗村円佳

  第12回近畿大学環境科学研究会  2013/08  第12回近畿大学環境科学研究会
  
• 長鎖ノンコーディングRNA, ANRILによる細胞増殖制御機構の解明  [Not invited]

  神武 洋二郎; 苗村円佳

  第50回化学関連支部合同九州大会  2013/07  第50回化学関連支部合同九州大会
  
• 癌化シグナルによって発現変動する長鎖非コードRNA,ANRILの機能解析  [Not invited]

  神武 洋二郎; 北川雅敏

  日本農芸化学会  2013/03  日本農芸化学会
  
• 慢性進行性腎障害におけるCks1およびSkp2の発現亢進の意義  [Not invited]

  鈴木小由里; 深澤洋敬; 三崎太郎; 戸川証; 北川恭子; 神武洋二郎; 山本龍夫; 北川雅敏

  第33回日本分子生物学会年会・第83回日本生化学大会合同大会  2012/12
• 人はなぜ老いるのか？～細胞老化研究から分かってきた老いのメカニズム  [Not invited]

  神武 洋二郎

  第53回近畿大学産業理工学部 公開講座  2012/10  福岡市  第53回近畿大学産業理工学部 公開講座
  
• Recent progress of long non-coding RNA research  [Not invited]

  神武 洋二郎; 医学部; 医学部

  第71回日本癌学会  2012/09  第71回日本癌学会
  
• Chk1 phosphorylates the tumor suppressor Mig-6, regulating the activation of EGF signaling  [Not invited]

  神武 洋二郎; 医学部; 医学部; 医学部; 医学部

  第45回日本発生生物学会・第64回日本細胞生物学会合同大会  2012/05  神戸  第45回日本発生生物学会・第64回日本細胞生物学会合同大会
  
• ヒトはなぜ老いるのか？～細胞老化研究とアンチエイジングへの応用～  [Not invited]

  神武 洋二郎

  近畿大学産業理工学部生物環境化学科特別講演会  2012/02  近畿大学産業理工学部生物環境化学科特別講演会
  
• 長鎖ノンコーディングRNA ANRILによる癌抑制遺伝子p15/p16の転写制御機構  [Not invited]

  神武 洋二郎

  第6回浜松医科学シンポジウム  2012/02  第6回浜松医科学シンポジウム
  
• The epigenetic regulation of INK4 locus by Polycomb and long noncoding RNA, ANRIL.  [Not invited]

  神武洋二郎; 中川直; 北川恭子; 鈴木小由里; 劉寧; 丹伊田浩行; Yue Xiong; 北川雅敏

  第34回日本分子生物学会年会  2011/12
• 癌化・老化を左右する新規非コードRNAの機能解析  [Not invited]

  神武洋二郎

  文部科学省,新学術領域研究, 「非コードRNA」領域班会議  2011/11
• 長鎖ノンコーディングRNA ANRILはポリコームリクルートメントを介してINK4遺伝子座を抑制する  [Not invited]

  神武洋二郎; 北川恭子; 丹伊田浩行; 北川雅敏

  第70回日本癌学会学術総会  2011/10
• 慢性進行性腎障害におけるNF-kB経路によるSkp2およびCks1の発現亢進  [Not invited]

  鈴木小由里; 深澤洋敬; 三崎太郎; 戸川証; 北川恭子; 神武洋二郎; 丹伊田浩行; 菱田明; 山本龍夫; 北川雅敏

  第84回日本生化学会大会  2011/09
• 長鎖ノンコーディングRNA ANRILによるポリコームリクルートメントを介したINK4 locus転写抑制機構  [Not invited]

  神武洋二郎; 中川直; 北川恭子; 鈴木小由里; 劉寧; 丹伊田浩行; Yue Xiong; 北川雅敏

  第84回日本生化学会大会  2011/09
• Long non-coding RNA ANRIL negatively regulates cell prolifereation via silencing of INK4 locus.  [Not invited]

  北川雅敏; 神武洋二郎

  第63回日本細胞生物学会大会  2011/06
• Long non-coding RNA ANRIL is required for the Polycomb recruitment to and silencing of INK4 locus.  [Not invited]

  Kotake Y; Nakagawa T; Kitagawa K; Niida H; Xiong Y; Kitagawa M

  Sixteenth Annual Meeting of the RNA Society  2011/06
• 長鎖ノンコーディングRNAによるINK4 locus制御機構  [Not invited]

  神武洋二郎; 中川直; 北川恭子; 丹伊田浩行; Yue Xiong; 北川雅敏

  第5回日本エピジェネティクス研究会年会  2011/05
• Polycomb/noncoding RNAによる癌抑制遺伝子p16転写制御機構の解明  [Invited]

  神武洋二郎

  第2回浜松医科学シンポジウム  2010/12
• 癌抑制遺伝子産物 Mig-6 のリン酸化とその責任酵素の解析  [Not invited]

  Ning Liu; 北川恭子; 神武洋二郎; 丹伊田浩行; 北川雅敏

  第33回日本分子生物学会年会・第83回日本生化学大会合同大会  2010/12
• GSK3 によるc-Mybの量的制御機構  [Not invited]

  北川恭子; 神武洋二郎; 北川雅敏

  第33回日本分子生物学会年会・第83回日本生化学大会 合同大会  2010/12
• CUL4-DDB1/MLL complex activates the p16 transcription through histone H3K4 methylation  [Not invited]

  神武洋二郎; Yue Xiong; 北川恭子; 北川雅敏

  第33回日本分子生物学会年会・第83回日本生化学大会合同大会  2010/12
• The epigenetic regulation of INK4 locus by Polycomb and noncoding RNA.  [Not invited]

  Kotake Y; Kitagawa K; Nakagawa T; Xiong Y; Kitagawa M

  2010/11
• 癌化・老化を左右する新規非コードRNAの機能解析  [Not invited]

  神武洋二郎

  文部科学省,新学術領域研究,「非コードRNA」 領域班会議  2010/10
• c-Mybの量的制御機構におけるGSK3の関与  [Not invited]

  北川恭子; 神武洋二郎; 北川雅敏

  第69回日本癌学会学術総会  2010/10
• CUL4A-DDB1 ubiquitin ligase and MLL histone methyltransferase are required for the oncogene-induced p16INK4a activation.  [Not invited]

  神武洋二郎; 北川恭子; 北川雅敏

  第69回日本癌学会学術総会  2010/10
• 細胞老化誘導のキーレギュレーター、p16の転写制御機構の解明  [Not invited]

  神武洋二郎; 北川恭子; Yue Xiong; 北川雅敏

  日本農芸化学会2010年度大会  2010/03
• 転写因子c-Mybのユビキチン-プロテアソームによる分解機構の解明  [Not invited]

  北川恭子; 神武洋二郎; 小田敏明; 北川雅敏

  日本薬学会第130年会  2010/03
• 細胞増殖を制御する新規長鎖ノンコーディングRNAの機能解析  [Not invited]

  小田敏雅; 高塚大輝; 神武洋二郎; 北川雅敏

  第3回浜松医科学シンポジウム  2010/02
• 癌抑制遺伝子p16 のヒストンメチル化を介した転写制御機構  [Invited]

  神武洋二郎

  第22回東北大学NM-GCOEセミナー  2010/01
• The epigenetic regulation of p16 tumor suppressor gene by Polycomb/MLL complex.  [Invited]

  神武洋二郎; 北川雅敏

  第32回日本分子生物学会年会  2009/12
• ポリコームタンパクによる精子幹細胞制御機構の全容解明  [Not invited]

  神武洋二郎

  文部科学省, 特定領域研究,「生殖系列」 領域班会議  2009/11
• ストレス誘導性小胞体:細胞質におけるタンパク質環境監視装置?  [Not invited]

  小田 敏明; 磯部 智康; 北川 恭子; 神武 洋二郎; 横田 貞記; 北川 雅敏

  第82回日本生化学会大会  2009/10
• Fbw7はGSK3によるリン酸化を介してc-Mybのユビキチン依存的分解を実行する  [Not invited]

  北川恭子; 中村悟己; 神武洋二郎; 北川雅敏

  第68回日本癌学会学術総会  2009/10
• Pirh2 is involved in human cancer malignancy as an E3 ubiquitin ligase for p27.  [Not invited]

  北川雅敏; 島田真衣; 土橋洋; 服部隆行; 神武洋二郎; 橋本賢; 北川恭子

  第68回日本癌学会学術総会  2009/10
• The epigenetic regulation of p16INK4a tumor suppressor gene.  [Not invited]

  神武洋二郎; 北川恭子; 北川雅敏

  第68回日本癌学会学術総会  2009/10
• Polycomb/MLL複合体によるヒストンメチル化を介したp16転写制御機構  [Not invited]

  神武洋二郎; Yue Xiong; 北川恭子; 磯部智康; 小田敏明; 北川雅敏

  第8回核ダイナミクス研究会  2009/06
• 浸透圧ストレスによるマウスTERT遺伝子の転写制御機構の解析  [Not invited]

  藤木司; 神武洋二郎; 三浦巧; 白畑實隆; 片倉喜範

  日本農芸化学会2008年度大会  2008/03
• NFAT5によるマウスTERT遺伝子制御機構の解析  [Not invited]

  藤木司; 神武洋二郎; 三浦巧; 白畑實隆; 片倉喜範

  第30回日本分子生物学会・第80回日本生化学会合同大会  2007/12
• pRB family proteins are required for polycomb repression complexes binding to and silencing p16.  [Not invited]

  Kotake Y; Cao R; Viatour P; Sage J; Zhang Y; Xiong Y

  Growth Factor and Signal Transduction Conferences  2007/07
• マウスTERT遺伝子の転写制御機構の解析  [Not invited]

  藤木司; 神武洋二郎; 三浦巧; 香月一志; 白畑實隆; 片倉喜範

  日本動物細胞工学会2007年度大会  2007/07
• 遺伝子改変マウスを用いたDNA含量と細胞サイズについての解析  [Invited]

  中山啓子; 神武洋二郎; 石田典子; 三宅智; 中山敬一

  第27回日本分子生物学会年会  2004/12
• ノックインマウスを用いた p27 の主要リン酸化部位であるセリン 10 リン酸化の機能解析  [Not invited]

  神武洋二郎; 中山啓子; 石田典子; 中山敬一

  第27回日本分子生物学会年会  2004/12
• Analysis of p27 knock-in mice harboring mutation on serine 10, a major phosphorylation site of p27.  [Not invited]

  Kotake Y; Nakayama K; Ishida N; Nakayama KI

  Coldspring Harbor Symposium (The Cell Cycle)  2004/05
• マウスTERT遺伝子の転写制御機構の解析  [Not invited]

  藤木司; 片倉喜範; 三浦巧; 神武洋二郎; 吉崎嘉一; 白畑実隆

  日本農芸化学会2004年度大会  2004/03
• マウスTERT遺伝子の転写制御機構の解析  [Not invited]

  藤木司; 片倉喜範; 三浦巧; 神武洋二郎; 吉崎嘉一; 白畑実隆

  第26回日本分子生物学会年会  2003/12
• 細胞内局在変化による p27 蛋白安定性の調節  [Invited]

  石田典子; 神武洋二郎; 中山啓子; 中山敬一

  第26回日本分子生物学会年会  2003/12
• ノックインマウスを用いたp27の主要リン酸化部位であるセリン10リン酸化の機能解析  [Not invited]

  神武洋二郎; 石田典子; 中山啓子; 中山敬一

  第26回日本分子生物学会年会  2003/12
• マウスTERT遺伝子転写制御機構の解析  [Not invited]

  藤木司; 片倉喜範; 三浦巧; 神武洋二郎; 山内ちひろ; 白畑実隆

  日本農芸化学会2003年度大会  2003/03
• ヒト及びマウスTERT遺伝子の転写制御機構の解析  [Not invited]

  藤木司; 片倉喜範; 三浦巧; 神武洋二郎; 吉崎嘉一; 白畑実隆

  日本農芸化学会2002年度大会  2002/03
• 細胞分化に伴うテロメラーゼ活性制御機構の解析  [Not invited]

  藤木司; 片倉喜範; 神武洋二郎; 三浦巧; 照屋輝一郎; 白畑実隆

  日本農芸化学会2001年度大会  2001/03
• テロメラーゼ触媒サブユニット遺伝子発現におけるTAK1/TAB1の関与  [Not invited]

  三浦巧; 片倉喜範; 西村修一; 神武洋二郎; 田平有紀子; 上原範久; 田代康介; 白畑実隆

  日本農芸化学会2001年度大会  2001/03
• ヒト及びマウステロラーゼ触媒サブユニット遺伝子の転写制御機構の解析  [Not invited]

  神武洋二郎; 片倉嘉範; 三浦巧; 上原範久; 田代康介; 照屋輝一郎; 白畑實隆

  日本農芸化学会2001年度大会  2001/03
• 細胞老化誘導におけるTAK1/TAB1の関与  [Not invited]

  三浦巧; 片倉喜師範; 西村修一; 神武洋二郎; 田平有紀子; 上原範久; 田代康介; 白畑實隆

  第23回日本分子生物学会年会  2000/12
• Differential regulation of TERT promoter between human and mouse cells  [Not invited]

  Kotake Y; Katakura Y; Miura T; Uehara N; Teruya K; Shirahata S

  The 13th international meeting of JAACT  2000/11

MISC

• Effect of 5’-Modification on the Asymmetry Recognition of siRNA and the Elimination of Off-Target Effect

  藤井政幸; 神武洋二郎; 塩浜康雄  日本薬学会年会要旨集(Web)  143rd-  2023
• 核酸医薬によるKRAS(G12D)の選択的発現制御

  藤井政幸; 神武洋二郎; 塩浜康雄  医療薬学フォーラム講演要旨集  31st-  2023
• 〈PAPERS and REPORTS〉Quantitative PCR Discriminating Single Base Mutation Using Phosphorothioate Primers

  園川 舞華; 久野 雅明; 藤田 崇史; 塩浜 康雄; 神武 洋二郎; 北山 隆; 柏﨑 玄伍; 藤井 政幸  かやのもり：近畿大学産業理工学部研究報告 = Reports of Faculty of Humanity-Oriented Science and Engineering, Kindai University  (32)  1  -8  2021/06
• 〈PAPERS and REPORTS〉Chemical Modification of siRNA Eliminating Off-target Effect by the Sense Strand

  塩浜 康雄; 藤田 崇史; 神武 洋二郎; 藤井 政幸  かやのもり：近畿大学産業理工学部研究報告 = Reports of Faculty of Humanity-Oriented Science and Engineering, Kindai University  (31)  13  -20  2020/06
• Selective Regulation of Mutant Oncogene KRAS (G12D) by siRNA

  塩浜 康雄; 藤田 崇史; 神武 洋二郎; 岡田 斉; 藤井 政幸  かやのもり : 近畿大学産業理工学部研究報告 = reports of School of Humanity-Oriented Science and Engineering, Kinki University  (30)  1  -7  2019
• Gene Silencing by miRNA-like siRNA

  新貝 恭広; 柏原 慎一; 藤井 啓史; 峰松 剛; 吉永 尚平; 苗村 円佳; 神武 洋二郎; 藤井 政幸  かやのもり : 近畿大学産業理工学部研究報告 : reports of School of Humanity-Oriented Science and Engineering, Kinki University  (25)  1  -6  2016
• 非小細胞肺癌においてY-box binding protein 1(YB-1)はサイクリンD1に直接結合し転写活性を亢進させる(YB-1 binds to and activates cyclinD1 transcriptional activities in Non-Small-Cell Lung Cancer)

  原田 雅教; 神武 洋二郎; 北川 恭子; 丹伊田 浩行; 椙村 春彦; 北川 雅敏  日本癌学会総会記事  73回-  P  -3092  2014/09
• ヒト非小細胞肺癌においてYB-1はサイクリンD1の転写を促進する(YB-1 promotes transcription of cyclin D1 in human non-small-cell lung cancers)

  原田 雅教; 神武 洋二郎; 大畑 樹也; 北川 恭子; 丹伊田 浩之; 松浦 駿; 船井 和仁; 椙村 春彦; 須田 隆文; 北川 雅敏  日本呼吸器学会誌  3-  (増刊)  185  -185  2014/03
• Long non-coding RNA and cellular senescence

  神武 洋二郎; 北川 雅敏  Cell technology  30-  (7)  729  -733  2011
• Research CDKインヒビターp27Kip1のタンパク質分解による制御機構

  神武 洋二郎; 中山 敬一  遺伝子医学  7-  (2)  231  -237  2003/06

Awards & Honors

• 2016 内藤記念科学振興財団 研究助成金
   

  受賞者: 神武洋二郎
• 2013 武田科学振興財団 医学系研究奨励
   

  受賞者: 神武洋二郎
• 2010 財団法人持田記念医学薬学振興財団 研究助成金
   

  受賞者: 神武洋二郎
• 2008 財団法人東京生化学研究会 研究奨励金
   

  受賞者: 神武洋二郎

Research Grants & Projects

• INK4遺伝子座から転写される新規長鎖ncRNAの癌抑制作用機構と生理機能の解明

  科学研究費補助金 基盤研究（C)：

  Date (from‐to) : 2022/04 -2025/03 

  Author : 神武洋二郎
• 頭頸部癌における新規バイオマーカーの開発

  科学研究費補助金 基盤研究（C)：

  Date (from‐to) : 2020/04 -2023/03 

  Author : 若崎高裕; 神武洋二郎
• 新規長鎖非コードRNAによるINK4遺伝子座制御とその破綻による発ガン機構の解明

  科学研究費補助金 基盤研究（C)：

  Date (from‐to) : 2017/04 -2020/03 

  Author : 神武洋二郎
• 長鎖非コードRNAによるエピジェネティクス制御機構の解明とその医学的応用

  財団法人内藤記念科学振興財団：内藤記念科学奨励金

  Date (from‐to) : 2016/04 -2018/03 

  Author : 神武洋二郎
• 癌化シグナルによって発現誘導される長鎖非コードRNAの機能解明とその阻害剤の探索

  科学研究費補助金 基盤研究（C)：

  Date (from‐to) : 2014/04 -2017/03 

  Author : 神武洋二郎
• 癌化に関与する機能性高分子非コードRNAの網羅的探索とその医学的応用

  財団法人武田科学振興財団：医学系研究奨励

  Date (from‐to) : 2013/04 -2015/03 

  Author : 神武洋二郎
• p53を制御する新規長鎖ノンコーディングRNAの機能解析

  科学研究費補助金 若手研究（B)：

  Date (from‐to) : 2012/04 -2014/03 

  Author : 神武洋二郎
• INK4遺伝子座制御機構とその破綻による発癌機構の解明

  科学研究費補助金 若手研究（B)：

  Date (from‐to) : 2010/04 -2012/03 

  Author : 神武洋二郎
• 癌化・老化を左右する新規非コードRNAの機能解析

  科学研究費補助金 新学術領域研究：

  Date (from‐to) : 2010/04 -2012/03 

  Author : 神武洋二郎
• 癌関連遺伝子の発現を制御するノンコーディングRNAの解析とその医学的応用

  財団法人持田記念医学薬学振興財団：研究助成金

  Date (from‐to) : 2010/04 -2011/03 

  Author : 神武洋二郎
• ポリコームタンパクによる精子幹細胞制御機構全容解明

  科学研究費補助金 特定領域研究：

  Date (from‐to) : 2009/04 -2011/03 

  Author : 神武洋二郎
• 癌化シグナルによるCDKインヒビターp16の転写活性化機構の解明

  財団法人東京生化学研究会：研究奨励金

  Date (from‐to) : 2008/12 -2009/12 

  Author : 神武洋二郎

Others

• 2017/04 -2020/03  核酸医薬による変異K-RAS遺伝子発現制御と革新的抗癌薬の開発 

  近畿大学学内研究助成金 研究種目: 21世紀研究開発奨励金[共同研究助成金] 課題番号: KD1704 研究内容: 核酸医薬を用いて変異K-RAS遺伝子の発現を選択的に抑制することにより、あるいは、抗変異K-RAS核酸医薬とセツキシマブ等のモノクロナール抗体医薬やエルロチニブ等の分子標的薬との併用により革新的な変異K-RAS依存性がんの治療薬を開発する。
• 2016/04 -2019/03  革新的統合ノンコーディングRNA研究による分子標的薬の開発 

  近畿大学学内研究助成金 研究種目：21世紀研究開発奨励金 [共同研究助成金] 課題番号：KD14 研究内容：本研究では、miRNA、siRNA、lncRNAを含む新規ガン関連ncRNAを探索し、その作動原理と生理機能を解明する。さらに得られた成果を基に、ncRNAを標的とした、従来とは異なる作用機序を持つガン治療薬開発へと展開するための研究基盤を確立する。

Other link

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https://researchmap.jp/2536