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2002 Fiscal Year Final Research Report Summary

Functional Study on a Novel Proapoptotic Protein of ASG

Research Project

Project/Area Number 12670109
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionSHINSHU UNIVERSITY

Principal Investigator

SAGARA Junji  Shinshu Universidy School of medicine, Associate Professor, 医学部, 助教授 (10225831)

Co-Investigator(Kenkyū-buntansha) TANIGUCHI Shunichiro  Shinshu Universidy School of Medicine, Professor, 医学部, 教授 (60117166)
Project Period (FY) 2000 – 2002
Keywordsapoptosis / ASC / PYRIN / caspase-1 / interleukine-1β / interleukine-18 / inflammation / innate immunity
Research Abstract

We showed that apoptosis-associated speck-like protein containing a Caspase recruitment domain (ASC) was an adaptor protein that was composed of two protein-protein interaction domains, a PYRIN domain, and a caspase-recruitment domain CARD. ASC belongs to a large family of proteins that contain a Pyrin, AIM, ASC, and death domain-like (PYRIN) domain (also known as PAAD and DAPIN). Recent data have suggested that ASC functions as an adaptor protein linking various PYRIN-family proteins to pathways involved in nuclear factor (NF)-kappaB and pro-Caspase-1 activation. Next, we focused on the expression of ASC in neutrophils. Immunohistochemical study showed that ASC is increased in neutrophils in severe inflammatory sites of gangrenous appendicitis. Also showed that ASC was increased in neutrophils exhibiting-characteristic phenotypes for apoptosis. These findings suggest that up-regulation of ASC is closely associated with inflammation and apoptosis in neutrophils. ASC also modulates diverse NF-kappaB induction pathways by acting upon the IKK complex, implying a broad role for this and similar proteins containing PYRIN domains in regulation of inflammatory responses.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Masumoto J.et al.: "PYrin N-terminal homology domain (PYD)-and a caspase recruitment domain (CARD) dependent oligomerization of ASC"Biochem.Biophys.Res.Comm.. 280. 652-655 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masumoto J.et al.: "Expression of apoptosis-associated speak-like protein containing CARD, a pyrin N-terminal homology domain, in human tissues"J.Histochem.Cytochem.. 49. 1269-1275 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shiohara M.et al.: "ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and apoptosis"Biochem.Biophys.Res.Comm.. 293. 1314-1318 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oguchi M.et al.: "Expression of lamins depends on epidermal differentiation and transformation"British J.Dermatol.. 147. 853-858 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Stehlik C.et al.: "The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in NF-κB activation pathway"J.Exp.Med.. 196. 1605-1615 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masumoto J.et al.: "Caspy, a zebrafish caspase activated by ASC Oligomerization required for pharyngeal arch development"J.Biol.Chem.. 278. 4268-4276 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masumoto J, Zhou W, Chen FF, Su F, Kuwada JY, Hidaka E, Katsuyama T, Sagara J, Taniguchi S, Ngo-Hazelett P, Postlethwait JH, Nunez G, and Inohara N.: "Caspy : A Zebrafish caspase activated by ASC oligomerization required for pharyngeal Arch development"J. Biol. Chem. 278. 4268-4276 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Stehlik C, Florentine L, Dorfleutner A, Bruey J, Ariza EM, Sagara J, and Reed JC.: "The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in NF-kB activation pathways."J. Exp. Med.. 196. 1605-1615 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oguchi M, Sagara J, Matsumoto K, Saida T, and Taniguchi S.: "Expression of lamins depends on epidermal differentiation and transformation."British J. Dermatol.. 147. 853-858 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiohara M, Taniguchi S, Masumoto J, Yasui K, Koike K, Komiyama A, and Sagara J.: "ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and apoptosis in human neutrophils."Biochem. Biophys. Res. Comm.. 293. 1314-1318 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeoka M, Ehara T, Sagara J, Hashimoto S, and Taniguchi S.: "Calponin hi induced a flattened morphology and suppressed the growth of human fibrosarcoma HT1080 cells."Eur. J .Cancer.. 38. 436-442 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masumoto J, Taniguchi S, NakayaniaJ, Shiohara M, Hidaka E, Katsuyama T, Murase S, and Sagara J.: "Expression of apoptosis-associated speck-like protein containing a caspase recruitment domain, a pyrin N-terminal homology domain-containing protein, in normal human tissues."J. Histochem. Cytochem.. 49. 1269-1275 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masumoto J, Taniguchi S, and Sagara J: "Pyrin N-terminal homology domain(PYD)-and caspase recruitment domain (CARD)-dependent oligomerization of ASC."Biochem. Biophys. Res. Comm.. 280. 652-655 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masumoto J, Taniguchi S, Nakayama K, Ayukawa K, and Sagara J.: "Murine ortholog of ASC, a CARD-containmg protein, self-associates and exhibits restricted distribution in developing mouse embryos."Exp. Cell. Res.. 262. 123-133 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ayukawa K, Taniguchi S, Masumoto J, Hashimoto S, Sarvotham H, Hara A, Aoyama T, and Sagara J.: "La autoantigen is cleaved in the COOH-terminus and loses the nuclear localization signal (NLS) during apoptosis."J. Biol. Chem.. 275. 34465-34470 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Xiao S, Komiya K, Tochikura TS, Sagara J, Tsukita S, and Kawai A.: "The rabies virion-associated 100-kDa polypeptide(VAP100) is a host-derived minor component of the viral envelope."Mcrobiol. Immunol.. 44. 657-668 (2000)

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      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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