Biology of the Ubiquitin System

2010 Fiscal Year Final Research Report

• Project Area: Proteolysis in the Regulation of Biological Processes
• Project/Area Number: 18076006
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Tsukuba
• Principal Investigator: CHIBA Tomoki University of Tsukuba, 大学院・生命環境科学研究科, 教授 (00311423)
• Project Period (FY): 2006 – 2010
• Keywords: ユビキチン / ユビキチン様タンパク質 / プロテアソーム / タンパク質分解

Research Abstract

The proteins in the body are in a dynamic state and they are continually degraded as well as synthesized. Selective protein degradation is regulated by an elaborate system called Ubiquitin-system. Ubiquitin is a small molecule that marks the proteins for proteasomal degradation. This selective protein degradation is essential for many cellular events and its impairment cause various diseases such as cancer and neurodegenerative diseases. The summary of this study is twofold. We identified and characterized several enzymes involved in the ubiquitination reaction mediated by Cullin-based ubiquitin ligase complexes (ie; substrate recognition, regulation of conjugation and de-conjugation, etc). Secondly, we generated mutant mice for one of the proteasome regulatory subunit to clarify the function of proteasome regulatory particles.

Research Products

• [Journal Article] The mechanism of poly-NEDD8 chain formation in vitro. (2009)
  • Author(s): Ooki Y, Konishi N, Funatsu N, Chiba T.
  • Journal Title: B.B.R.C. 381 Pages: 443-447
  • Peer Reviewed
• [Journal Article] PML activates transcription by protecting HIPK2 and p300 from SCFFbx3-mediated degrada -tion. (2008)
  • Author(s): Shima Y, Shima T, Chiba T, Irimura T, Pandolfi PP, Kitabayashi I.
  • Journal Title: Mol Cell Biol. 28 Pages: 7126-7138
  • Peer Reviewed
• [Journal Article] A novel ubiquitin ligase involved in p57^<Kip2> proteolysis regulates osteoblast cell differentiation. (2008)
  • Author(s): Kim M, Nakamoto K, Nishimori S, Tanaka K, Chiba T.
  • Journal Title: EMBO rep. 9 Pages: 878-884
  • Peer Reviewed
• [Journal Article] Allele-selective effect of PA28 in MHC class I antigen processing. (2008)
  • Author(s): Yamano T, Sugahara H, Mizukami S, Murata S, Chiba T, Tanaka K, Udono H.
  • Journal Title: J.Immunol. 181 Pages: 1655-1664
  • Peer Reviewed
• [Journal Article] Muscle RING-finger protein-1 (MuRF1) as a connector of muscle energy metabolism and protein synthesis. (2008)
  • Author(s): Koyama S, Hata S, Witt CC, Ono Y, Lerche S, Ojima K, Chiba T, Doi N, Kitamura F, Tanaka K, Abe K, Witt SH, Rybin V, Gasch A, Franz T, Labeit S, Sorimachi H.
  • Journal Title: J Mol Biol. 376 Pages: 1224-1236
  • Peer Reviewed
• [Journal Article] SCRAPPER- Dependent Ubiquitination of Active Zone Protein RIM1 Regulates Synaptic Vesicle Release. (2007)
  • Author(s): Yao I, Takagi H, Ageta H, Kahyo T, Sato S, Hatanaka K, Fukuda Y, Chiba T, Morone N, Yuasa S, Inokuchi K, Ohtsuka T, MacGregor GR, Tanaka K, Setou M.
  • Journal Title: Cell 130 Pages: 943-957
  • Peer Reviewed
• [Journal Article] Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. (2007)
  • Author(s): Ohtake F, Baba A, Takada I, Okada M, Iwasaki K, Miki H, Takahashi S, Kouzmenko A, Nohara K, Chiba T, Fujii-kuriyama Y, Kato S.
  • Journal Title: Nature 446 Pages: 562-566
  • Peer Reviewed
• [Journal Article] TBP-interacting protein 120b(TIP120B)/cullin-associated and neddylation-dissociated 2 (CAND2) inhibits SCF-dependent ubiquitination of myogenin and accelerates myogenic differentiation. (2007)
  • Author(s): Shiraishi S, Zhou C, Aoki T, Sato N, Chiba T, Tanaka K, Yoshida S, Nabeshima Y, Nabeshima Y, Tamura TA.
  • Journal Title: J Biol Chem. 282 Pages: 9017-9028
  • Peer Reviewed
• [Journal Article] Direct interactions between NEDD8 and ubiquitin E2 conjugating enzymes upregulate cullin-based E3 ligase activity. (2007)
  • Author(s): Sakata E, Yamaguchi Y, Miyauchi Y, Iwai K, Chiba T, Saeki Y, Matsuda N, Tanaka K, Kato K.
  • Journal Title: Nat.Struct.Mol.Biol. 14 Pages: 167-168
  • Peer Reviewed
• [Presentation] A mutation in an AdRP causative gene affects its Cullin complex formation. (2010)
  • Author(s): Kigoshi Y, Tsuruta F, Chiba T.
  • Organizer: American Society of Cell Biology Meeting.
  • Place of Presentation: Philadelphia, U.S.A
  • Year and Date: 20101211-20101215
• [Presentation] Loss of Parkin leads to selective degeneration of spermatogonia in mice. (2010)
  • Author(s): Komatsu T, Satake T, Sato A, Tsuruta F, Chiba T.
  • Organizer: 日本分子生物学会、日本生化学会合同年会
  • Place of Presentation: 神戸市、神戸ポートアイランド
  • Year and Date: 20101207-20101210
• [Presentation] The analyses of the poly-NEDD8 chain. (2010)
  • Author(s): Takashima O, Tsuruta F, Funatsu N, Konishi N, Chiba T.
  • Organizer: The 6^<th> International Conferences on COP9 Signalosome, Proteasome and eIF3. ZOMES VI.
  • Place of Presentation: Safed, Israel.
  • Year and Date: 20101001-20101010
• [Remarks] ホームページ等
  • URL: http://tchibalab.org/