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Study of cyclin E-Cdk2 interacting proteins

Research Project

Project/Area Number 09680682
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionKurume University

Principal Investigator

OOTSUBO Motoaki  Kurume University, Institute of Life Science, Assistant, 分子生命科学研究所, 助手 (10211799)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordscell cycle / CDK / cyclin-dependent kinase / cyclin E / E3 ubiquitin protein-ligase / E6AP / Cdk2 / 細胞がん化 / p21 / Zincフィンガー
Research Abstract

Cyclin E-Cdk2 is an evolutionary conserved G1 Cyclin-dependent kinase (CDK) that is specifically required for the initiation of DNA replication. The activity of cyclin E-Cdk2 in G1 phase is mainly regulated by CDK inhibitors (CKLs), like p21 and p27. An E6-AP like HECT (homologous to the E6-AP carboxyl terminus) family gene encoding a putative E3 ubiquitin-protein ligase was isolated by a two-hybrid screening using both cyclin E and p21, as the bait. This gene named Ceb 1 (cyclin E-binding protein) possesses RCC1 (regulator of chromosome condensation) -like repeats besides the HECT domain, and encodes a 117-kd cytoplasmic protein that can interact with various cyclins in mammalian cells, and can be phosphorylated by the Cdk2 kinases. Expression of Cebi was specifically detected in testis and ovary among various human tissues and highly elevated Ceb1 expression was exclusively limitted in tissue culture cells containing defective tumor suppressor proteins, p53 and pRB.Consistently, inactivation of these tumor suppressors by viral oncoproteins like SV4O T antigen and human papillomavirus(HPV) type 16, E6 or E7 markedly induced the Ceb1 message in primary human fibroblasts. Furthermore, the expression of Ceb1 was induced by the treatment with histone deacetylase inhibitors and through cell's population doubling, and the Cebl expression induced by SV4O T antigen was repressed by ectopic overexpression of the adenovirus p53.
Cyclin E expression levels is inversely correlated with the Cebl expression levels. Cells expressing Ceb1 at high levels exhibited low cyclin E protein levels, and vice versa. Forced overexpression of the cyclin E message in cells expressing Ceb1 at high levels did not allow overexpression of cycilin E protein unlike cells expressing Ceb1 at low levels.Thus, Ceb1 likely mediates the regulation of cyclin E expression in testis and in p53 and pRB defective cells.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Ikezawa, K.et al.: "Role of cyclin E and cyclin E-dependent kinase in mitogenic stimulation by cementum-derived growth factor in human fibroblasts." FASEB J.12,12. 1233-1239 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuji, T.et al.: "Cyclin E overexpression responsible for growth of human hepatic tumors with p21WAF1/CIP1/SDI1." Biochem.Biophys.Res.Commun.242,2. 317-321 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yokouchi M.et al.: "APS, an adaptor protein containg PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis." Oncogene. 18,3. 759-767 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanimura S, et al.: "MDM2interacts with MDMX through their RING finger domains." FEBS Lett.in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sakamoto H, et al.: "A Janus kinase inhibitor, JAB, is an interforon-γ-inducible gene and confers resistance to interferons." Blood. 92,5. 1668-1676 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Misawa H, et al.: "Cloning and characterization of a novel class II phosphoinositide 3-kinase containing C2 domain." Biochem.Biophys.Res.Commun.244,2. 531-539 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikezawa, K.et al.: "Role of cyclin E and cyclin E-dependent : kinase in mitogenic stimulation by cementum-derived growth factor in human fibroblasts." FASEBJ. 12(12). 1233-1239 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuji, T.et al.: "Cyclin E overexpression responsible for growth of human hepatic tumors with p21WAF1/CIP1/SDI1." Biochem Biophys.Res.Commun.242(2). 317-321 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yokouchi M,et al.: "APS,an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cb1 and inhibits PDGF-induced mitogenesis." Oncogene. 18(3). 759-767 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanimura S,et al.: "MDM2 interacts with MDMX through their RING finger domains." FEBS Lett.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sakamoto H,et al.: "A Janus kinase inhibitor, JAB,is an interferon-gamma-inducible gene and confers resistance to interferons." Blood. 92(5). 1668-1676 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Misawa H,et al.: "Cloning and characterization of a novel class II phosphoinositide 3-kinase containing C2 domain." Biochem Biophys.Res.Commun.244(2). 531-539 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikezawa,K et al.: "Role of cyclin E and cyclin E-dependent kinase in mitogenic stimulation by cementum-derived growth factor in human fibroblasts." FASEB J.12,12. 1233-1239 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuji,T.et al.: "Cyclin E overexpression responsible for growth of human hepatic tumors with p21WAF1/CIP1/SDI1." Biochem.Biophys.Res.Commun.242,2. 317-321 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yokouchi M,et al.: "APS,an adaptor protein containing PH and SH2 domains,is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis." Oncogene. 18,3. 759-767 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanimura S,et al.: "MDM2 interacts with MDMX through their RING finger domains." FEBS Lett.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakamoto H,et al.: "A Janus kinase inhibitor,JAB,is an interferon-γ-inducible gene and confers resistance to interferons." Blood. 92,5. 1668-1676 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Misawa H,et al.: "Cloning and characterization of a novel class II phosphoinositide 3-kinase containing C2 domain." Biochem.Biophys.Res.Commun.244,2. 531-539 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuji T,et al.: "Cyclin E overexpression responsible for growth of human hepatic tumors with p21WAF1/CIP1/SDI1" Biochem.Biophys.Res.Commun.242・2. 317-321 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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