The analysis of the correlation between the increase of Pirh2 expression and cancer progress

• Project/Area Number: 21590062
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: KITAGAWA Kyoko 浜松医科大学, 医学部, 助教 (20299605)
• Co-Investigator(Kenkyū-buntansha): KITAGAWA Masatoshi 浜松医科大学, 医学部, 教授 (50294971)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 分子生物学 / Pirh2 / タンパク分解 / ユビキチン化 / 癌 / タナパク分解

Research Abstract

The protein level of Pirh2 was affected by the post translation regulation system under a DNA stress condition. In the search process of novel substrates of Pirh2, we discovered c-Myb as a novel degradation target of Fbw7. GSK3 activity regulated the c-Myb protein level, although it was suggested that its function was different from a mouse in human.

Research Products

• [Journal Article] Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15^<INK4B> tumor suppressor gene (2011)
  • Author(s): Kotake, Y., Nakagawa, T., Kitagawa, K., Suzuki, S., Liu, N., Kitagawa, M. and Xiong, Y.
  • Journal Title: Oncogene Volume: 30(16) Pages: 1956-62
• [Journal Article] Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of P15INK4B tumor suppressor gene. (2011)
  • Author(s): Kotake, Y., et al.
  • Journal Title: Oncogene Volume: 30 Issue: 16 Pages: 1110-1120
  • DOI: 10.1038/onc.2010.568
  • Peer Reviewed
• [Journal Article] Up-regulation of Cksl and Skp2 with TNFcx/NFkB signaling in chronic progressive nephropathy. (2011)
  • Author(s): Suzuki, S., et al.
  • Journal Title: Genes Cells Volume: 16 Issue: 11 Pages: 1110-1120
  • DOI: 10.1111/j.1365-2443.2011.01553.x
  • Peer Reviewed
• [Journal Article] GSK3 regulates the expression of human and mouse c-Myb via different mechanisms (2010)
  • Author(s): Kitagawa, K., Kotake, Y., Hiramatsu, Y., Liu, N., Suzuki, S., Nakamura, S., Kikuchi, A. and Kitagawa, M.
  • Journal Title: Cell Div Volume: 5(27)
  • NAID: 120005305355
• [Journal Article] Formation of acetaldehyde-derived DNA adducts due to alcohol exposure (2010)
  • Author(s): Yu, Hs., Oyama, T., Isse, T., Kitagawa, K., Pham, T. T., Tanaka, M. and Kawamoto, T.
  • Journal Title: Chem Biol Interact Volume: 188(3) Pages: 367-75
• [Journal Article] Aldehyde dehydrogenase 2 knockout accentuates ethanol-induced cardiac depression : Role of protein phosphatases (2010)
  • Author(s): Ma, H., Yu, L., Byra, EA., Hu, N., Kitagawa, K., Nakayama, KI., Kawamoto, T and Ren, J.
  • Journal Title: J Mol Cell Cardiol Volume: 49(2) Pages: 322-9
• [Journal Article] Reduction of transforming growth factor-beta type II receptor is caused by the enhanced ubiquitin-dependent degradation in human renal cell carcinoma (2010)
  • Author(s): Fukasawa, H., Yamamoto, T., Fujigaki, Y., Misaki, T., Ohashi, N., Takayama, T., Suzuki, S., Mugiya, S., Oda, T., Uchida, C., Kitagawa, K., Hattori, T., Hayashi, H., Ozono, S., Kitagawa, M. and Hishida, A.
  • Journal Title: Int J Cancer Volume: 127 Pages: 1517-25
• [Journal Article] GSK3 regulates the expression of human and mouse c-Myb via different mechanisms. (2010)
  • Author(s): Kitagawa, K., et al.
  • Journal Title: Cell Division Volume: 5 Pages: 1-10
  • NAID: 120005305355
  • Peer Reviewed
• [Journal Article] Formation of acetaldehyde-derived DNA adducts due to alcohol exposure. (2010)
  • Author(s): Yu, H., et al.
  • Journal Title: Chem Biol Interact. Volume: 188 Pages: 367-375
  • Peer Reviewed
• [Journal Article] Aldehyde dehydrogenase 2 knockout accentuates ethanol-induced cardiacdepression : Role of protein phosphatases. (2010)
  • Author(s): Ma, H., et al.
  • Journal Title: J Mol Cell Cardiol. Volume: 49 Pages: 322-329
  • Peer Reviewed
• [Journal Article] Reduction of transforming growth factor-ss type II receptor is caused by theenhanced ubiquitin-dependent degradation in human renal cell carcinoma. (2010)
  • Author(s): Fukasawa, H., et al.
  • Journal Title: Int.J.Cancer Volume: 127 Pages: 1517-1525
  • Peer Reviewed
• [Journal Article] Kaposi's sarcoma-associated herpesvirus- encoded LANA positively affects on ubiquitylation of p53. (2010)
  • Author(s): Suzuki, T., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 403 Pages: 194-197
  • Peer Reviewed
• [Journal Article] Hepatocyte Growth Factor stimulated cell scattering requires ERK and Cdc42-dependent Tight Junction Disassembly. (2010)
  • Author(s): Togawa, A., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 400 Pages: 271-277
  • Peer Reviewed
• [Journal Article] Dual mode of regulation of Cdc25A protein by TRB3. (2010)
  • Author(s): Sakai, S., et al.
  • Journal Title: Biol.Pharm.Bull. Volume: 33 Pages: 1112-1116
  • Peer Reviewed
• [Journal Article] p27 modulates tropism of mesenchymal stem cells toward brain tumors. (2010)
  • Author(s): Gao, Y., et al.
  • Journal Title: Exp.Ther.Med. Pages: 695-699
  • Peer Reviewed
• [Journal Article] Characteristics of aldehyde dehydrogenase 2(Aldh2) knockout mice (2009)
  • Author(s): Yu, HS, Oyama, T, Isse, T, Kitagawa, K., Ogawa, M., Pham, T. T. and Kawamoto, T.
  • Journal Title: Toxicol. Mechanisms and Methods Volume: 19(9) Pages: 535-40
• [Journal Article] Cholinergic alterations following alcohol exposure in the frontal cortex of Aldh2-deficient mice models (2009)
  • Author(s): Jamal, M., Ameno, K., Miki, T., Wang, W., Kumihashi, M., Isse, T, Kawamoto, T., Kitagawa, K, , Nakayama, K., Ijiri, I and Kinoshita, H.
  • Journal Title: Brain Res Volume: 1295 Pages: 37-43
• [Journal Article] Adenovirus E1A inhibits SCF^<Fbw7> ubiquitin ligase (2009)
  • Author(s): Isobe, T., Hattori, T., Kitagawa, K., Uchida, C., Kotake, Y., Kosugi, I., Oda, T. and Kitagawa, M.
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 27766-79
• [Journal Article] Ubiquitin-mediated control of oncogene and tumor suppressor gene products (2009)
  • Author(s): Kitagawa, K., Kotake, Y. and Kitagawa, M.
  • Journal Title: Cancer Sci Volume: 100(8) Pages: 1374-81
  • NAID: 10027192844
• [Journal Article] Fbw7 promotes ubiquitin-dependent degradation of c-Myb : involvement of GSK3-mediated phosphorylation of Thr-572 in mouse c-Myb (2009)
  • Author(s): Kitagawa, K., Hiramatsu, Y., Uchida, C., Isobe, T., Hattori, T., Oda, T., Shibata, K., Nakamura, S., Kikuchi, A. and Kitagawa, M.
  • Journal Title: Oncogene Volume: 28(25) Pages: 2393-405
• [Journal Article] Decrease in TRADD resulted from ubiquitin-dependent degradation in the obstructive renal injury in rats. Am (2009)
  • Author(s): Misaki, T., Yamamoto, T., Suzuki, S., Fukasawa, H., Togawa, A., Ohashi, N., Suzuki, H., Fujigaki, Y., Oda, T., Uchida, C., Kitagawa, K., Hattori, T., Kitagawa, M. and Hishida, A.
  • Journal Title: J. Pathol Volume: 175(1) Pages: 74-83
• [Journal Article] High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers (2009)
  • Author(s): Shimada, M., Kitagawa, K., Dobashi, Y., Isobe, T., Hattori, T., Uchida, C., Abe, K., Kotake, Y., Oda, T., Suzuki, H., Hashimoto, K. and Kitagawa, M.
  • Journal Title: Cancer Sci Volume: 100(5) Pages: 866-72
  • NAID: 10025145601
• [Journal Article] Decrease in TRADD resulted from ubiquitin-dependent degradation in the obstructive renal injury in rats (2009)
  • Author(s): Misaki, T., et al.
  • Journal Title: Am.J.Pathol. 175 Pages: 74-83
  • Peer Reviewed
• [Journal Article] Fbw7 promotes ubiquitin-dependent degradation of c-Myb : involvement of GSK3-mediated phosphorylation of Thr-572 in mouse c-Myb (2009)
  • Author(s): Kitagawa, K., et al.
  • Journal Title: Oncogene 28 Pages: 2393-405
  • Peer Reviewed
• [Journal Article] Ubiquitin-mediated control of oncogene and tumor suppressor geneproducts (2009)
  • Author(s): Kitagawa, K., et al.
  • Journal Title: Cancer Sci. 100 Pages: 1374-81
  • NAID: 10027192844
  • Peer Reviewed
• [Journal Article] Adenovirus E1A inhibits SCF^<FbW7> ubiquitin ligase (2009)
  • Author(s): Isobe, T., et al.
  • Journal Title: J.Biol.Chem. 284 Pages: 27766-79
  • Peer Reviewed
• [Journal Article] Ethanol metabolism in ALDH2 knockout mice-Blood acetate levels (2009)
  • Author(s): Ameno K., et al.
  • Journal Title: Legal Med. 11 Pages: 413-5
  • Peer Reviewed
• [Journal Article] Cholinergic alterations following alcohol exposure in the frontal cortex of Aldh2-deficient mice models (2009)
  • Author(s): Jamal M., et al.
  • Journal Title: Brain Res. 1295 Pages: 37-43
  • Peer Reviewed
• [Presentation] ヒトおよびマウスc-Mybタンパク量調節におけるGSK3βの異なる関与 (2011)
  • Author(s): 北川恭子
  • Organizer: 日本血液学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] The epigenetic regulation of INK4 locus by Polycomb and long noncoding RNA, ANRIL (2011)
  • Author(s): 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
  • Organizer: 第34回日本分子生物学会年会
• [Presentation] 増殖分化制御因子のタンパク量調節機構の解析 (2011)
  • Author(s): 北川恭子, 中村悟己, 北川雅敏
  • Organizer: 第73回日本血液学会学術集会
• [Presentation] 増殖シグナルの新たな制御機構 (2010)
  • Author(s): 北川雅敏, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] 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 (2010)
  • Author(s): Ning Liu, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] CUL4-DDB1/MLL complex activates the p16 transcription through histone H3K4 methylation (2010)
  • Author(s): Yojiro Kotake, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] 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 (2010)
  • Author(s): 鈴木小由里, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] GSK3によるc-Mybの量的制御機構 (2010)
  • Author(s): 北川恭子, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] A novel target and function of Chkl (2010)
  • Author(s): Masatoshi Kitagawa
  • Organizer: MEXT Priority Research Project "Cell Proliferation Control" International Symposium Cell Cycle and Cell Differentiation From A to Z
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-06
• [Presentation] CUL4A-DDB1ユビキチンリガーゼとMLLヒストンメチルトランスフェラーゼは癌化シグナルによるP16転写活性化に必要である (2010)
  • Author(s): 神武洋二郎, 他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] c-Mybの量的制御機構におけるGSK3の関与 (2010)
  • Author(s): 北川恭子, 他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] GSK3によるc-Mybの量的制御機構 (2010)
  • Author(s): 北川恭子, 神武洋二郎, 北川雅敏
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
• [Presentation] 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 (2010)
  • Author(s): Ning Liu,北川恭子,神武洋二郎,丹伊田浩行,北川雅敏
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
• [Presentation] CUL4-DDB1/MLL complex activates the p16 transcription through histone H3K4 methylation (2010)
  • Author(s): Yojiro Kotake、Xiong Yue, Kyoko Kitagawa, Masatoshi Kitagawa
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
• [Presentation] 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 (2010)
  • Author(s): 鈴木小由里,深沢洋敬,三崎太郎,戸川証,北川恭子,神武洋二郎,山本龍夫,北川雅敏
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
• [Presentation] c-Mybの量的制御機構におけるGSK3の関与 (2010)
  • Author(s): 北川恭子, 神武洋二郎, 北川雅敏
  • Organizer: 第69回日本癌学会学術総会
• [Presentation] CUL4A-DDB1ユビキチンリガーゼとMLLヒストンメチルトランスフェラーゼは癌化シグナルによるP16転写活性化に必要である (2010)
  • Author(s): 神武洋二郎,北川恭子,北川雅敏
  • Organizer: 第69回日本癌学会学術総会
• [Presentation] 転写因子c-Mybのユビキチン-プロテアソームシステムによる分解機構の解明 (2010)
  • Author(s): 北川恭子, 神武洋二郎, 小田敏明, 北川雅敏
  • Organizer: 日本薬学会第130年会
• [Presentation] 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 (2010)
  • Author(s): 神武洋二郎,北川恭子, Xiong Yue,北川雅敏
  • Organizer: 日本農芸化学会2010年度大会
• [Presentation] SCF-Fbw7 E3 ligase targets c-Myb for GSK3-dependent degradation (2009)
  • Author(s): 北川恭子, 平松良浩, 磯部智康, 柴田清, 中村悟己, 北川雅敏
  • Organizer: 第32回日本分子生物学会年会
• [Presentation] Regulation of c-Myb by Fbw7 via ubiquitin-proteasome-dependent degradation (2009)
  • Author(s): 北川恭子, 中村悟己,北川雅敏
  • Organizer: 第71回日本血液学会学術集会
• [Presentation] 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 (2009)
  • Author(s): 北川恭子, 中村悟己, 神武洋二郎, 北川雅敏
  • Organizer: 第68回日本癌学会学術総会
• [Presentation] エピジェネティックなp16転写制御機構 (2009)
  • Author(s): 神武洋二郎,北川恭子,北川雅敏
  • Organizer: 第68回日本癌学会学術総会
• [Presentation] Pirh2はp27のユビキチンリガーゼとしてヒトの癌の悪性度に関与する (2009)
  • Author(s): 北川雅敏,島田真衣,土橋洋,服部隆行,神武洋二郎,橋本賢二,北川恭子
  • Organizer: 第68回日本癌学会学術総会
• [Remarks]
  • URL: http://www2.hama-med.ac.jp/w1a/bio1/index-j.html
• [Remarks]
  • URL: http://www.hama-med.ac.jp/uni_education_igakubu_igaku_seika1.html
• [Remarks]
  • URL: http://www2.hama-med.ac.jp/wla/biol/index-j.html
• [Patent(Industrial Property Rights)] 癌治療用組成物 (2012)
  • Inventor(s): 北川雅敏、高芸、北川恭子
  • Industrial Property Rights Holder: 浜松医科大学
  • Industrial Property Number: 2007-528119
  • Acquisition Date: 2012-02-16
• [Patent(Industrial Property Rights)] 癌の転移性及び浸潤能の検査方法 (2006)
  • Inventor(s): 北川雅敏、高芸、北川恭子
  • Industrial Property Rights Holder: 浜松医科大学
  • Acquisition Date: 2006-04-14