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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
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsapoptosis / ASC / PYRIN / caspase-1 / interleukine-1β / interleukine-18 / inflammation / innate immunity / NF-KB / 炎症疾患 / Pyrin / Toll-like receptor / 感染 / 細胞死 / ガン / メチレーション / pyrin / CARD
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.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumoto J.et al.: "PYPIN N-terminal homdogy domain (PYD)-and a caspase recruitment domain dependent digomerization of ASC"Biochem. Biophys. Res. Comm.. 280. 652-655 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masumoto J.et al.: "Expression of apoptosis associated speck-like protein containing CARD, a pyrin N-terminal homdogy domain, in human tissues"J. Histochem. Cytochem.. 49. 1269-1275 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shiohara M.et al.: "ASC, which is composed of a PYD and a CARD, is up-requleted by inflammation and apoptosis"Biochem. Biophys. Res. Comm.. 293. 1314-1318 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oguchi M.et al.: "Expression of lamins depends on epidermal differentiation and transformation"British J. Dermatol.. 147. 853-858 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Stehlik C.et al.: "THE PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in NF-KB activation pathway"J. Exp. Med.. 196. 1605-1615 (2002)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeoka M, 〜: "Calponin h1 induced a flattened morphology and suppressed the growth of human fibrosarcoma HT1080 cells"Eur J Cancer. 38(3). 436-442 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masumoto J, 〜: "Expression of apoptosis-associated speak-like protein containing a caspase recruitment domain, a pyrin N-terminal homology domain-containing protein, in normal human tissues"J Histochem Cytochem. 49(10). 1269-1275 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniguchi S, 〜: "Structural fragility of blood vessels and peritoneum in calponin h1-deficient mice, resulting in an increase in hematogenous metastasis and peritoneal dissemination of malignant tumor cells"Cancer Res. 61. 7627-7634 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masumoto J, 〜: "Pyrin N-Terminal Homology Domain- and Caspase Recruitment Domain-Dependent Oligomerization of ASC"BBRC. 280. 652-655 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masumoto J, 〜: "Murine ortholog of ASC, a regulator of apoptosis, exhibits restricted distribution in developing mouse embryos"Exp Cell Res. 262. 123-133 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ayukawa K, 〜: "La autoantigen is cleaved in the COOH-terminus and loses the nuclear localization signal (NLS) during apoptosis"J Biol Chem. 275. 34465-34470 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masumoto J, 〜: "Pyrin N-Terminal Homology Domain- and Caspase Recruitment Domain-Dependent Oligomerization of ASC."BBRC. 280. 652-655 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masumoto J, 〜: "Murine ortholog of ASC, a regulator of apoptosis, exhibits restricted distribution in developing mouse embryos."Exp Cell Res. 262. 123-133 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ayukawa K, 〜: "La autoantigen is cleaved in the COOH-terminus and loses the nuclear localization signal (NLS) during apoptosis."J Biol Chem. 275. 34465-34470 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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