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Study on the novel S-phase specific proteolysis pathway

Research Project

Project/Area Number 18570181
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionUniversity of Hyogo (2007)
Kyushu University (2006)

Principal Investigator

NISHITANI Hideo  University of Hyogo, Grad. Sch. of Life Sci, Professor (40253455)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsCell Cycle / Aroteolvsis / replication / ubiauitin / PCNA / DNA複製
Research Abstract

Cdt1, an essential factor for DNA replication licensing, is degraded soon after entry into S-phase. We discovered that two ubiquitin ligases, Skp2-Cul1 and DDB1-Cul4, independently recognize the N-terminus of Cdt1 for ubiquitination. The first 10 amino acid region of Cdt1 contains a conserved sequence, PCNA interacting motif (PIP-box). During S-phase, PCNA and DDB1-Cul4 co-operate to ubiquitinate Cdt1. This system also operates after DNA damage, such as UV irradiation. When PIP-box was mutated, Cdt1 became stable after UV irradiation, and during S-phase combined with silencing of Skp2. Many PCNA interacting proteins were isolated. Among them, we found that CDK inhibitor p21 is also degraded through PCNA and DDB1-Cul4 system. Though both Cdt1 and p21 play key roles during G1-phase, their presence after initiation of S-phase is not suitable for proper cell cycle progression., and thus should be degraded upon entry into S-phase. We propose that PCNA dependent DDB1-Cul4 ubiquitin system provides a feedback system that helps the coordination between end of G1-phase and initiation of S-phase.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (25 results)

All 2007 2006

All Journal Article (18 results) (of which Peer Reviewed: 8 results) Presentation (6 results) Book (1 results)

  • [Journal Article] Geminin cleavage during apoptosis by caspase-3 alters its binding ability to the SWI/SNF subunit Brahma2007

    • Author(s)
      Roukos V, et. al.
    • Journal Title

      J Biol Chem 282

      Pages: 9346-9357

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Cdtl associates dynamically with chromatin throughout G1 and recruits Geminin onto chromatin2007

    • Author(s)
      Xouri G, et. al.
    • Journal Title

      EMBO J. 26

      Pages: 1303-1314

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Licensing regulators Geminin and Cdtl identify progenitor cells of the mouse CNS in a specific phase of the cell cycle2007

    • Author(s)
      Spella M, et. al.
    • Journal Title

      Neuroscience 147

      Pages: 373-387

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Geminin cleavage during apoptosis by caspase-3 alters its binding ability to the SWI/SNF subunit Brahma2007

    • Author(s)
      Roukos V, Iliou, MS, Nishitani H, Gentzel M, Wilm M, Taraviras S, Lygerou, Z
    • Journal Title

      J Biol Chem 282(13)

      Pages: 9346-9357

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cdtl associates dynamically with chromatin throughout GI and recruits Geminin onto chromatin2007

    • Author(s)
      Xouri G, Squire A, Dimaki M, Geverts B, Verveer, PJ, Taraviras S, Nishitani H, Houtsmuller, AB, Bastiaens, PI, Lygerou, Z
    • Journal Title

      EMBO J 26(5)

      Pages: 1303-1314

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Licensing regulators Geminin and Cdt1 identify progenitor cells of the mouse CNS in a specific phase of the cell cycle2007

    • Author(s)
      Spella M, Britz O, Kotantaki P, Lygerou Z, Nishitani H, Ramsay, RG, Flordellis C, Guillemot F, Mantamadiotis T, Taraviras, S
    • Journal Title

      Neuroscience 147(2)

      Pages: 373-387

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Control of pre-RC formation and prevention of re-replication through regulating licensing factor Cdtl2007

    • Author(s)
      Nishitani, H
    • Journal Title

      Experimental Medicine 25

      Pages: 31-36

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Geminin cleavage during apoptosis by caspase-3 alters its binding ability to the SWI/SNF subunit Brahma2007

    • Author(s)
      Roukos V, et. al.
    • Journal Title

      J Biol Chem. 282

      Pages: 9346-9357

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cdt1 associates dynamically with chromatin throughout Gl and recruits Geminin onto chromatin.2007

    • Author(s)
      Xouri G, et. al.
    • Journal Title

      EMBO J. 26

      Pages: 1303-1314

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Licensing regulators Geminin and Cdt1 identify progenitor cells of the mouse CNS in a specific phase of the cell cycle.2007

    • Author(s)
      Spella M, et. al.
    • Journal Title

      Neuroscience 147

      Pages: 373-387

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a heat-shock protein Hsp40, DjB1, as an acrosome-and a tail-associated component in rodent spermatozoa.2007

    • Author(s)
      Doiguchi M et al.
    • Journal Title

      Mol Reprod Dev. 74

      Pages: 223-232

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Temperature-sensitive defects of the GSP1gene, yeast Ran homologue, activate the Tell-dependent pathway.2007

    • Author(s)
      Hayashi N et al.
    • Journal Title

      Biochem Biophys Res Commun. 353

      Pages: 330-336

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdtl for proteolysis2006

    • Author(s)
      Nishitani H, et. al.
    • Journal Title

      EMBO J. 25

      Pages: 1126-1136

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Nuclear RanGAP is required for the heterochromatin assembly and is reciprocally regulated by histone H3 and C1r4 histone methyltransferase in Schizosaccharomyces pombe2006

    • Author(s)
      Nishijima, et. al.
    • Journal Title

      Mol.Biol.Cell 17

      Pages: 2524-2536

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis2006

    • Author(s)
      Nishitani H, Sugimoto N, Roukos V, Nakanishi Y, Saijo M, Obuse C, Tsurimoto T, Nakayama, KI, Nakayama K, Fujita M, Lygerou Z, Nishimoto, T
    • Journal Title

      EMBO J 25

      Pages: 1126-1136

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Nuclear RanGAP is required for the heterochromatin assembly and is reciprocally regulated by histone H3 and C1r4 histone methyltransferase in Schizosaccharomyces pombe2006

    • Author(s)
      Nishijima H, Nakayama J, Yoshioka T, Kusano A, Nishitani H, Shibahara K, Nishimoto, T
    • Journal Title

      Mol. Biol. Cell 17

      Pages: 2524-2536

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis2006

    • Author(s)
      Nishitani H et al.
    • Journal Title

      EMBO J. 25

      Pages: 1126-1136

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nuclear RanGAP is required for the heterochromatin assembly and is reciprocally regulated by histone H3 and Clr4 histone methyltransferase in Schizosaccharomyces pombe.2006

    • Author(s)
      Nishijima et al.
    • Journal Title

      Mol.Biol.Cell 17

      Pages: 2524-2536

    • Related Report
      2006 Annual Research Report
  • [Presentation] ライセンス化因子Cdt1の分解機構と染色体複製の制御2007

    • Author(s)
      西谷 秀男, 他
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Proteolysis of Licensing Factor Cdt1 and its role on DNA replication2007

    • Author(s)
      Nishitani H, Shiomi Y, Iida H, Lygerou, Z
    • Organizer
      BMB
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 染色体複製のライセンス化因子Cdt1の制御機構の解析2006

    • Author(s)
      西谷 秀男, 他
    • Organizer
      日本分子生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      2006-12-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Tsurimoto, TControl on the DNA replication Licensing factor Cdt12006

    • Author(s)
      Nishitani H, Iida H, Sugimoto N, Fujita M, Lygerou Z
    • Organizer
      MBSJ Forum
    • Place of Presentation
      Nagoya
    • Year and Date
      2006-12-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Two ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdtl for proteolysis2006

    • Author(s)
      西谷 秀男, 他
    • Organizer
      20th IUBMB
    • Place of Presentation
      京都
    • Year and Date
      2006-06-23
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdtl for proteolysis2006

    • Author(s)
      Nishitani H, Sugimoto N, Roukos V, Nakanishi Y, Saijo M, Obuse C, Tsurimoto T, Fujit M, Lygerou Z, Nishimoto T
    • Organizer
      IUBMB
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-23
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 染色体サイクル Cdt1タンパク質によるpre-RC形成と再複製の抑制制御2007

    • Author(s)
      西谷 秀男
    • Total Pages
      6
    • Publisher
      実験医学羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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