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cDNA cloning and functional analysis of a signal transducer, TRAF5

Research Project

Project/Area Number 09670341
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionJuntendo University School of Medicine

Principal Investigator

NAKANO Hiroyasu  Dept.Immunol., Juntendo Univ.Sch.Med., Asst.Prof, 医学部, 助手 (70276476)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsTRAF / NF-kappaB / NF-kappaB-inducing kinase / IkappaB kinase / MEKK1 / ASK1 / knockout mice / CD40 / NF-kB / NF-kB-inducing kinase / IkB kinase / MEKKI / ASKI / Lymphotoxin-βレセプター / CD27 / CD30 / NF-κB. / JNK / ERK
Research Abstract

1. We demonstrated that TRAF2 and TRAF5 interact with CD27 and CD3O, and are involved in NF-kappaB activation by these receptors. We also determined the binding domain of CD27 and CD3O for TRAF2 and TRAF5.
2. Recently, NF-kappaB kinase (NIK) was identified and has been shown to activate two subunits of the 1kappaB kinase complex, IKKalpha and IKKbeta, both of which directly phosphorylate IkappaBs. We demonstrated that while NIK activates IKKalpha and IKK3b comparably, MEKKI preferentially activates IKKbeta.
3. We showed that upon TNF treatment, TRAF2 interacts with apoptosis-regulating kinase 1 (ASK 1) and ASK1 is essential for TRAF2-mediated TNK/SAPK activation.
4. To determined the function of TRAF5 in vivo, we generated TRAF5-deficient mice. Despite of no defect of TNF-, CD27-, or CD4O-mediated activation of NF-kappaB or JNK/SAPK in TRAF5-deficient mice, CD4O- and CD27-mediated lymphocyte activation were impaired. These results suggest that a novel function of TRAF5, which is independent on activation of NF-kappaB or JNK/SAPK.

Report

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

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Nakano, H., et al.: "Human TNF receptor-associated factor 5 (TRAF5) : cDNA cloning, expression and assignmnet of TRAF5 gene to chromosome 1q32." Genomics. 42. 26-32 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aizawa, S., et al.: "Tumor Necrosis Factor Receptor-associated Factor (TRAF) 5 and TRAF2 Are Involved in CD30-mediated NF-κB Activation." J.Biol.Chem.272. 1-4 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishitoh, H., M.et al.: "ASK1 is essential for JNK/SAPK activation by TRAF2." Molecular Cell. 2. 389-395 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shindo, M., et al.: "Assignment of IκB kinase β (IKBKB) to human chromosome band 8p12-p11 by in situ hybridization." Cytogenet. Cell Genet.82. 32-33 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Akiba, H., et al.: "CD27, a member of the TNF receptor superfamily, activates NF-κB and Stress-activated Protein kinase/c-Jun N-terminal Kinase via TRAF2, TRAF5 and NF-κB-inducing kinase (NIK)." J.Biol.Chem.273. 13353-13358 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shindo, M., et al.: "cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2." Biochem.Biophys. Res.Com.244. 285-292 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakano, H., et al.: "Differential regulation of IKKα and IKKβ by two upstream kinases, NF-κB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1." Proc.Natl.Acad.Sci.95. 3537-3542 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oshima, H., et al.: "Characterization of murine CD70 by molecular cloning and mAb." Int.Immunol.10. 517-526 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kashiwada, M., et al.: "Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Stimulates Extracellular Signaling Kinase (ERK) Activity in CD40 Signaling Along a Ras-independent Pathway." J.Exp.Med.187. 237-244 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hatakeyama S., et al.: "Ubiquitin-dependent degradation of IκB is mediated by a novel ubiquitin ligase SCF^<FWD1>." Proc.Natl.Acad.Sci.USA. (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] Nakano, H., M.Shindo, K.Yamada, M.C.Yoshida, S.M.Santee, C.F.Ware, N.A.Jenkins, D.J.Gilbert, H.Yagita, N.G.Copeland, and K.Okumura.: "Human TNF receptor-associated factor 5 (TRAF5) : cDNA cloning, expression and assignmnet of TRAF5 gene to chromosome 1q32." Genomics. 42. 26-32 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aizawa, S., H.Nakano, T.Ishida, R.Horie, M.Nagai, K.Ito, H.Yagita, K.Okumura, J.Inoue, and T.Watanabe.: "Tumor Necrosis Factor Receptor-associated Factor (TRAF) 5 and TRAF2 Are Involved in CD30-mediated NF-kappaB Activation." J.Biol.Chem.272. 1-4 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishitoh, H., M.Saitoh, Y.Mochida, K.Takeda, H.Nakano, M.Rothe, K.Miyazono, and H.Ichijo.: "ASK1 is essential for JNK/SAPK activation by TRAF2." Molecular Cell. 2. 389-395 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shindo, M., H.Nakano, S.Sakon, H.Yagita, M.Mihara, and K.Okumura.: "Assignment of IkappaB kinase beta (IKBKB) to human chromosome band 8p12-p11 by in situ hybridization." Cytogenet.Cell Genet.82. 32-33 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Akiba, H., H.Nakano, S.Nishinaka, M.Shindo, T.Kobata, C.Morimoto, C.F.Ware, N.L.Malinin, D.Wallach, H.Yagita, and K.Okumura.: "CD27, a member of the TNF receptor superfamily, activates NF-kappaB and Stress-activated Protein kinase/c-Jun N-terminal Kinase via TRAF2, TRAF5 and NF-kappaB-inducing kinase (NIK)." J.Biol.Chem.273. 13353-13358 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shindo, M., H.Nakano, H.Kuroyanagi, T.Shirasawa, M.Mihara, D.J.Gilbert, N.A.Jenkins, N.G.Copeland, H.Yagita, and K.Okumura.: "cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2." Biochem.Biophys.Res.Com.244. 285-292 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakano, H., M.Shindo, S.Sakon, S.Nishinaka, M.Mihara, H.Yagita, and K.Okumura.: "Differential regulation of IKKalpha and IKKbeta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1." Proc.Natl.Acad.Sci.95. 3537-3542 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oshima, H., H.Nakano, C.Nohara, T.Kobata, A.Nakajima, N.A.Jenkins, D.J.Gilbert, N.G.Copeland, T.Muto, H.Yagita, and K.Okumura.: "Characterization of murine CD70 by molecular cloning and mAb." Int.Immunol.10. 517-526 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kashiwada, M., Y.Shirakata, J.-I.Inoue, H.Nakano, K.Okazaki, K.Okumura, T.Yamamoto, H.Nagaoka, and T.Takemori.: "Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Stimulates Extracellular Signaling Kinase (ERK) Activity in CD40 Signaling Along a Ras-independent Pathway." J.Exp.Med.187. 237-244 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hatakeyama S., M.Kitagawa, K.Nakayama, M.Shirane, M.Matasumoto, K.Hattori, H.Higashi, H.Nakano, K.Okumura, K.Onoe, R.A.Good, and K.-I.Nakayama.Proc.Natl.Acad.Sci.USA: "Ubiquitin-dependent degradation of IkappaB is mediated by a novel ubiquitin ligase SCF^<FWD1>." (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishitoh, H., M.et al.: "ASKI is essential for JNK/SAPK activation by TRAF2." Molecular Cell. 2. 389-395 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shindo, M., et al.: "Assignment of IkB kinaseβ (IKBKB) to human chromosome band 8p12-p11 by in situ hybridization." Cytogenet. Cell Genet.82. 32-33 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akoba, H., et al.: "CD27, a member of the TNF receptor superfamily, activates NF-kB and Stress-activated Protein Kinase/c-Jun N-terminal Kinase via TRAF2, TRAF5 and NF-kB-inducing Kinase(NIK)." J.Biol. Chem.273. 13353-13358 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shindo, M., et al.: "cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related Kinase(ARK)1 and 2." Biochem. Biophys. Res.Com.244. 285-292 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakano, H., et al.: "Differential regulation of IKKα and IKKβ by two upstream Kinases, NF-kB-inducing Kinase and mitogen-activated protein Kinase/ERK Kinase Kinase-1." Proc.Natl.Acad.Sci.95. 3537-3542 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oshima, H., et al.: "Characterization of murine CD70 by molecular cloning and mAb." Int.Immunol.10. 517-526 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kashiwada, M., et al.: "Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Stimulates Extracellular Signaling Kinase (ERK) Activity in CD40 Signaling Along a Ras-independent Pathway." J.Exp.Med.187. 237-244 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hatakeyama S., et al.: "Ubiquitin-dependent degradation of IkB is mediated by a novel ubiquitin ligase SCF^<FWD1>." Proc.Natl.Acad.Sci.USA. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakano,H.: "Differential regulation of IKKα and IKKβ by two upstream kinases,NIK and MEKK1." Proc.Natl.Acad.Sci.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oshima,H.: "Characterization of murine CD70 by molecular cloning and mAb." Int.Immunol.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kashiwada,M.: "Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Stimulates Extracellular Signaling Kinase (ERK) Activity in CD40 Signaling Along a Ras-independent Pathway." J.Exp.Med.187. 237-244 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakano,H.: "Human TNF receptor-associated factor 5 (TRAF5) : cDNA cloning,expression and assignment of TRAF5 gene to chromosome lq32." Genomics. 42. 26-32 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aizawa,S.: "Tumor Necrosis Factor Receptor-associated Factor (TRAF) 5 and TRAF2 Are Involved in CD30-mediated NF-κB Activation." J.Biol.Chem.272. 1-4 (1997)

    • Related Report
      1997 Annual Research Report

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

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