Analysis of diversity of ubiquitin ligase

• Project Area: Proteolysis in the Regulation of Biological Processes
• Project/Area Number: 18076001
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nagoya University
• Principal Investigator: TAKUMI Kamura (KAMURA Takumi) Nagoya University, 理学研究科, 教授 (40333455)
• Co-Investigator(Kenkyū-buntansha): SHIGETSUGU Hatakeyama 北海道大学, 大学院・医学研究科, 教授 (70294973)
• Project Period (FY): 2006 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥140,900,000 (Direct Cost: ¥140,900,000); Fiscal Year 2010: ¥30,000,000 (Direct Cost: ¥30,000,000); Fiscal Year 2009: ¥30,000,000 (Direct Cost: ¥30,000,000); Fiscal Year 2008: ¥30,000,000 (Direct Cost: ¥30,000,000); Fiscal Year 2007: ¥30,000,000 (Direct Cost: ¥30,000,000); Fiscal Year 2006: ¥20,900,000 (Direct Cost: ¥20,900,000)
• Keywords: タンパク質分解 / ユビキチン

Research Abstract

Ubiquitylation and subsequent proteasomal degradation of regulatory proteins control a variety of cellular processes. The ubiquitin conjugation to target proteins is processed by three enzymes, E1, E2, and E3. The E3s are responsible for recognizing and recruiting target proteins for polyubiquitylation. Cullin-based E3 complexes and TRIM E3 families are thought to regulate many cellular events. In this research, we try to clarify the function of Cullin-based E3 complexes and TRIM E3 families. Now we show that Cullin-based E3 complexes are responsible for regulating the function of Mrc1, Ctf4, Elongin A, p53, and Ypt53. We also identify that Lag2 negatively modulate the activity of SCF complex. Finally, we demonstrate that TRIM E3 families control the function of estrogen receptor, androgen receptor, Abi2, p53, PIAS3 and Ikkγ. These observations thus idicate that Cullin-based E3 complexes and TRIM E3 families plays an important role in a variety of cellular processes by regulating the function of many target proteins.

Research Products

• [Journal Article] Non-SCF type F-box protein Roy1/Ymr258c interacts with a Ra b5-like G TPase Yp t52 a nd inhibits Ypt52 function. (2011)
  • Author(s): Liu, Y., Nakatsukasa, K., Kotera, M., Kanada, A., Nishimura, T., Kishi, T., Mimura, S., Kamura, T.
  • Journal Title: Mol.Biol.Cell 22 Pages: 1575-1584
  • Peer Reviewed
• [Journal Article] Non-SCF type F-box protein Roy1/Ymr258c interacts with a Rab5-like GTPase Ypt52 and inhibits Ypt52 function (2011)
  • Author(s): Liu Y, et al
  • Journal Title: Molecular Biology of the Cell Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] MDA-9/syntenin interacts with ubiquitin via a novel ubiquitin-binding motif. (2011)
  • Author(s): Okumura F, et al
  • Journal Title: Mol Cell Biochem Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] RNF43 interacts with NEDL1 and regulates p53-mediated transcription. (2011)
  • Author(s): Shinada K, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 404 Pages: 143-147
  • Peer Reviewed
• [Journal Article] Cul8/Rtt101 forms a variety of protein complexes that regulate DNA damage response and transcriptional silencing. (2010)
  • Author(s): Mimura, S., Yamaguchi, T., Ishii, S., Noro, E ., Katsura, T., Obuse, C ., Kamura, T.
  • Journal Title: J.Biol.Chem. 285 Pages: 9858-9867
  • Peer Reviewed
• [Journal Article] TRIM8 modulates STAT3 activity through negative regulation of PIAS3 (2010)
  • Author(s): Okumura, F., Matsunaga, Y., Katayama, Y., Nakayama, K.I., Hatakeyama, S.
  • Journal Title: J.Cell.Sci. 123 Pages: 2238-2245
  • Peer Reviewed
• [Journal Article] TRIM8 modulates STAT3 activity through negative regulation of PIAS3. (2010)
  • Author(s): Okumura F, et al
  • Journal Title: J Cell Sci Volume: 123 Pages: 2238-2245
  • Peer Reviewed
• [Journal Article] Cu18/Rtt101 forms a variety of protein complexes that regulate DNA damage response and transcriptional silencing. (2010)
  • Author(s): Mimura S, et al
  • Journal Title: J.Biol.Chem. 2851 Pages: 9858-9867
  • Peer Reviewed
• [Journal Article] SCFDia2 regulates DNA replication forks during S-phase in budding yeast. (2009)
  • Author(s): Mimura, S., Komata, M ., K ishi, T., Shirahige, K., Kamura, T.
  • Journal Title: EMBO J. 28 Pages: 3693-3705
  • Peer Reviewed
• [Journal Article] A longevity protein, Lag2, interacts with SCF complex and regulates SCF function. (2009)
  • Author(s): Liu, Y., Mimura, S., Kishi, T., Kamura, T.
  • Journal Title: EMBO J. 28 Pages: 3366-3377
  • Peer Reviewed
• [Journal Article] Degradation of phosphorylated p53 by viral protein-ECSE3 ligase complex. (2009)
  • Author(s): Sato, Y., Kamura, T., Shirata, N., Murata, T., Kudoh, A., Iwahori, S., Nakayama, S., Isomura, H., Nishiyama, Y., Tsurumi T.
  • Journal Title: PLoS Pathog. 5(7)
  • Peer Reviewed
• [Journal Article] SCF^<Dia2> regulates DNA replication forks during S-phase in budding yeast. (2009)
  • Author(s): Mimura S, et al
  • Journal Title: EMBO J 28 Pages: 3693-3705
  • Peer Reviewed
• [Journal Article] A longevity protein, Lag2, interacts with SCF complex and regulates SCF function. (2009)
  • Author(s): Liu Y, et al
  • Journal Title: EMBO J 28 Pages: 3366-3377
  • Peer Reviewed
• [Journal Article] Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex. (2009)
  • Author(s): Sato Y, et al
  • Journal Title: PLoS Pathog 5
  • Peer Reviewed
• [Journal Article] TRIM 36 interacts with the kinetochore protein CENP-H and delays cell cycle progression (2009)
  • Author(s): Miyajima N, et.al.
  • Journal Title: Biochem. Biophys. Res. Commun 387 Pages: 383-387
  • Peer Reviewed
• [Journal Article] Inhibition of NF-κB signaling via tyrosine phosphorylation of Ymer (2009)
  • Author(s): Kameda H, et.al.
  • Journal Title: Biochem. Biophys. Res. Commun 378 Pages: 44-749
  • Peer Reviewed
• [Journal Article] Riplet/RNF 135, a RING-finger protein, ubiquitinates RIG-I to promote interferon-β induction during the early phase of viral infection (2009)
  • Author(s): Oshiumi H, et.al.
  • Journal Title: J. Biol. Chem 280 Pages: 5611-5621
  • Peer Reviewed
• [Journal Article] Mammalian Elongin A complex mediates DNA-damage-inducedu biquitylation and degradation of Rpb1. (2008)
  • Author(s): Yasukawa, T., Kamura, T., Kitajima, S., Conaway, RC., Conaway, JW., Aso, T.
  • Journal Title: EMBO J. 27 Pages: 3256-3266
  • Peer Reviewed
• [Journal Article] TRIM32 facilitates cell growth and migration via degradation of Abl-interactor 2 (2008)
  • Author(s): Kano, S., Miyajima, N., Fukuda, S., Hatakeyama, S.
  • Journal Title: Cancer Res. 68 Pages: 5572-5580
  • Peer Reviewed
• [Journal Article] TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells (2008)
  • Author(s): Miyajima, N., Maruyama, S., Bohgaki, M., Kano, S., Shigemura, M., Shinohara, N., Nonomura, K., Hata keyama, S.
  • Journal Title: Cancer Res. 68 Pages: 3486-3494
  • Peer Reviewed
• [Journal Article] TRIM32 facilitates cell growth and migration via degradation of Abl-interactor 2 (2008)
  • Author(s): Kano, S.,, Miyajima, N., Fukuda, S. and Hatakeyama, S.
  • Journal Title: Cancer Res. 68 Pages: 5572-5580
  • Peer Reviewed
• [Journal Article] Mammalian Elongin A complex mediates DNA-damage-induced ubiquitylation and degradation of Rpb1. (2008)
  • Author(s): Yasukawa, T., Kamura, T., Kitajima, S., Conaway, RC., Conaway, JW., Aso T.
  • Journal Title: EMBO J. 27 Pages: 3256-66
  • NAID: 120001871683
  • Peer Reviewed
• [Journal Article] TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells (2008)
  • Author(s): Miyajima, N., Maruyama, S., Bohgaki, M., Kano, S., Shigemura, M., Shinohara, N., Nonomura, K. and Hatakeyama, S.
  • Journal Title: Cancer Res. 68 Pages: 3486-3494
  • Peer Reviewed
• [Journal Article] Ro52 functionally interacts with IgG1 and regulates its quality control via the ERAD system (2008)
  • Author(s): Takahata, M., Bohgaki, M., Tsukiyama, T., Kondo, T., Asaka, M. and Hatakeyama, S.
  • Journal Title: Mol.Immunol. 45 Pages: 2045-2054
  • Peer Reviewed
• [Journal Article] Ubiquitylation of ε-COP by PIRH2 and regulation of the secretion of PSA (2008)
  • Author(s): Maruyama, S., Miyajima, N., Bohgaki, M., Tsukiyama, T., Shigemura, M., Nonomura, K. and Hatakeyama, S.
  • Journal Title: Mol.Cell.Biochem. 307 Pages: 73-82
  • Peer Reviewed
• [Journal Article] Mammalian Elongin A complex mediates DNA-damage-induced ubiquitylation and degradation of Rpb 1 (2008)
  • Author(s): Yasukawa T, et.al.
  • Journal Title: EMBO J 27 Pages: 3256-3266
  • Peer Reviewed
• [Journal Article] TRIM 32 facilitates cell growth and migration via degradation of Ab 1-interactor 2 (2008)
  • Author(s): Kano S, et.al.
  • Journal Title: Cancer Res 68 Pages: 5572-5580
  • Peer Reviewed
• [Journal Article] TRIM 68 regulates ligand-dependept transcription of androgen receptor in prostate cancer cells (2008)
  • Author(s): Niyajima N, et.al.
  • Journal Title: Cancer Res 68 Pages: 3486-3494
  • Peer Reviewed
• [Journal Article] TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells. (2008)
  • Author(s): Miyajima, N, et. al.
  • Journal Title: Cancer Res (in press)
  • Peer Reviewed
• [Journal Article] Involvement of Ymer in suppression of NF-κB activation by regulated interaction with lysine-63-linked polyubiquitin chain. (2008)
  • Author(s): Bohgaki, M, et. al.
  • Journal Title: BBA-Mol. Cell Res 1784 Pages: 826-837
  • Peer Reviewed
• [Journal Article] Ro52 functionally interacts with IgG1 and regulates its quality controlvia the ERAD system. (2008)
  • Author(s): Takahata, M, et. al.
  • Journal Title: Mol. Immunol. 45 Pages: 2045-2054
  • Peer Reviewed
• [Journal Article] Ubiquitylation of ε-COP by PIRH2 and regulation of the secretion of PSA (2008)
  • Author(s): Maruyama, S, et. al.
  • Journal Title: Mol. Cell. Biochem. 307 Pages: 73-82
  • Peer Reviewed
• [Journal Article] Involvement of Rabring7 in EGF receptor degradation as E3 ligase (2007)
  • Author(s): Sakane, A, et. al.
  • Journal Title: Biochem. Biophys. Res. Commun. 357 Pages: 1058-1064
  • Peer Reviewed
• [Journal Article] Ligand-dependent transcription of estrogen receptor α is mediated by the ubiquitin ligase EFP (2007)
  • Author(s): Nakajima, A, et. al.
  • Journal Title: Biochem. Biophys. Res. Commun 357 Pages: 245-251
  • Peer Reviewed
• [Journal Article] Establishment of a newly improved detection system for NF-κB activity. (2007)
  • Author(s): Matsuda, M
  • Journal Title: Immunol. Lett. 109 Pages: 175-181
  • Peer Reviewed
• [Journal Article] Fbxw8 is essential for Cul1-Cul7 complex formation and for placental development (2006)
  • Author(s): Tsunematsu, R et al.
  • Journal Title: Mol. Cell. Boil. 26 Pages: 6157-6169
• [Journal Article] Fbxw7 contributes to tumor suppression by targeting multiple proteins for ubiquitin-dependent degradation (2006)
  • Author(s): Fujii, Y et al.
  • Journal Title: Cancer Sci. 97 Pages: 729-736
• [Presentation] ユビキチンリガーゼの制御機構 (2010)
  • Author(s): 嘉村巧
  • Organizer: ユビキチンシンポジウム
  • Place of Presentation: 東京(シンポジウム)
  • Year and Date: 2010-08-21
• [Presentation] Alongevity protein, Lag2, interactswith SCF complex and regulates SCFfunction. (2010)
  • Author(s): Takumi K amura, Yuan Liu
  • 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
  • Place of Presentation: 神戸(シンポジウム)
• [Presentation] A longevityprotein, Lag2, interacts with SCF complex and regulates SCF function. (2010)
  • Author(s): 嘉村巧, 等
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Regulatory mechanisms for the membrane extraction of polytopic ERAD substreate at a post-ubiquitination step. (2010)
  • Author(s): 中務邦雄, 等
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] ECV^<VHL>複合体によって分解される新規基質の同定 (2010)
  • Author(s): 金森正和, 等
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] ECV^<VHL>複合体のユビキチンシステムにおける機能解析 (2010)
  • Author(s): 中野きりは, 等
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 出芽酵母F-boxタンパク質Met30の機能解析 (2009)
  • Author(s): 日置灯美, 等
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 出芽酵母SCFDia2によるDNA複製フォークの制御 (2009)
  • Author(s): 三村覚, 等
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 膜タンパク質の小胞体関連分解(ERAD)の生化学的および遺伝学的手法による解析 (2009)
  • Author(s): 中務邦雄, 等
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] P 80, a novel Cdc 53 interacting protein, regulates the function of SCF complex (2008)
  • Author(s): Liu Y, et.al.
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] 安定なDNA複製に関わる出芽酵母F-box蛋白質Dia2の解析 (2008)
  • Author(s): 三村覚, 等
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] 出芽酵母F-boxタンパク質Met30の機能解析 (2008)
  • Author(s): 三國恭平, 等
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] 出茅酵母F-box蛋白質Dia2と複製フォーク蛋白質との結合 (2007)
  • Author(s): 三村 覚 等
  • Organizer: 第30回日本分子生物学会年会.第80回日本生化学会大会.合同大会
  • Place of Presentation: 横浜
• [Presentation] 転写伸長因子Elongin AのRNA polymerase IIユビキチン化への関与 (2007)
  • Author(s): 安川 孝史 等
  • Organizer: 第30回日本分子生物学会年会.第80回日本生化学会大会.合同大会
  • Place of Presentation: 横浜
• [Presentation] 出茅酵母Cul8,MMS1,MMS22の複合体形成の解析 (2007)
  • Author(s): 石井 哲 等
  • Organizer: 第30回日本分子生物学会年会.第80回日本生化学会大会.合同大会
  • Place of Presentation: 横浜
• [Presentation] 細胞増殖抑制因子p27の新たな分解因子の分離精製及び解析 (2006)
  • Author(s): 嘉村巧、中山敬一
  • Organizer: 日本分子生物学会2006フォーラム
  • Place of Presentation: 名古屋(シンポジウム)
  • Year and Date: 2006-12-07
• [Presentation] VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitinligases. (2006)
  • Author(s): Kamura T
  • Organizer: The Fourth NIBB-EMBL Symposium Biology of Protein Conjugation, Structure and Function
  • Place of Presentation: 岡崎
  • Year and Date: 2006-12-04
• [Presentation] ユビキチンシステムと発癌・細胞周期 (2006)
  • Author(s): 嘉村巧
  • Organizer: 第68回日本血液学会総会・第48回日本臨床血液学会総会・合同総会
  • Place of Presentation: 福岡(教育講演)
  • Year and Date: 2006-10-07
• [Book] モノユビキチン化の解析 実験医学(別冊) タンパク質の翻訳後修飾解析プロトコール(稲垣昌樹編) (2006)
  • Author(s): 嘉村巧
  • Publisher: 羊土社、東京
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