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Molecular analysis of novel PDZ domain-containing gene encoding autoantigen of autoimmune enteropathy

Research Project

Project/Area Number 10670698
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

HOSOKAWA Masuo (1999)  Hokkaido University, School of Medicine, Professor, 医学部, 教授 (20001901)

外木 秀文 (1998)  北海道大学, 医学部, 助手 (50281803)

Co-Investigator(Kenkyū-buntansha) ODAGAWA Yasuhisa  Hokkaido University, Medicine Hosipital, Assis. Pro., 医学部・付属病院, 助手 (50292024)
SAKIYAMA Yukio  Hokkaido University, School of Medicine, Visiting Professor, 医学部(寄附講座), 教員 (80133734)
MORIUCHI Tetsuya  Hokkaido University, School of Medicine, Professor, 医学部, 教授 (20174394)
KOBAYASHI Ryouji  Hokkaido University, Medicine Hosipital, Assis. Pro., 医学部・付属病院, 助手 (30301899)
細川 真澄男  北海道大学, 医学部, 教授 (20001901)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsenteropathy / AIE-75 / PDZ domain / yeast / Wnt pathway / MCC / PDZドメイン蛋白 / Two-hybridアッセイ / 蛋白間相互作用 / 大腸癌 / 自己免疫性腸炎
Research Abstract

Autoimmune enteropathy (AIE) is a rare disorder characterized by protracted diarrhea unresponsive to diet therapy or total parenteral nutrition. Complementary DNA (cDNA) clones were isolated by immunoscreening a human duodenal cDNA-expression library with serum from a patient with X-linked autoimmune enteropathy (AIE). The cDNA encodes the 75-kilodalton antigen (AIE-75), and the composite nucleotide sequence of the cDNA for AIE-75 was 2214 bp long and encoded 552 amino acids. The deduced amino acid sequence contained 3 conserved PSD-95/Dlg/ZO-1 (PDZ) domains. AIE-75 was predominantly distributed in the epithelial cells of the luminal surface and the upper half of the crypts of the intestine and in the proximal renal tubulus. Using AIE-75 as a bait cDNA in yeast two-hybrid system, we isolated MMC (mutated in colon cancer) homologue MMC-2. The amino acid sequence of MCC-2 is 40% identical to that of MCC. We further isolated several cDNA clones which have been known to be members of Wnt signal pathway. Overexpression of AIE-75 in mammalian cells incresed the nuclear protein level of beta-catenin.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 細川眞澄男: "Increased E1AF expression in mouse fibrosarcoma promotes metastasis through industion of MT1-MMP expression"Oncogene. 18. 1771-1776 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 守内哲也: "Identification of an autoimmune enteropathy-related 75-kilodalton antigen"Gastroenterology. 117. 823-830 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 守内哲也: "Somatic mutations of the APC gene in primary breast cancers"Am.J.Pathol.. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 守内哲也: "Dominant negative mutations of the tumor suppressor p53 relating to early onset of glioblastoma multiforme"Cancer Res.. 59. 4765-4769 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 守内哲也: "A functional and quantitative mutational analysis of F53 mutations in yeast indicates strand biases and different roles of mutations in DMBA-and BBN-induced tumors"Int.J.Cancer. 83. 700-705 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 崎山幸雄: "Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency"Blood. 91. 30-36 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Habelhah, H., Okada, F., Kobayashi, M., Nakai, Choi, S., Hamada, J., Moriuchi T., Kaya, M., Yoshida, K., Fujinaga, K. and Hosokawa, M.: "Increased EIAF expression in mouse fibrosarcoma promotes metastasis through induction of MT l-MMP expression."Oncogene. 18. 1771-1776 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi, I., Imamura, K., Kubota, M., Ishikawa, S., Yamada, M., Tonoki, H., Okano, M., Storch, W.B., Moriuchi, T., Sakiyama, Y., Kobayashi, K.: "Identification of an autoimmune enteropathy-rel ated 75-kilodalton antigen."Gastroenterology. 117. 823-830 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ftiruuchi, K., Tada, M., Yamada, H., Kataoka, A., Furuuchi, N., Hamada, J., Takahashi, M., Todo, S. and Moriuchi, T.: "Somatic Mutations of the APC gene in Primary Breast Cancers."Am. J. Pathol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Marutanl, M., Tonoki, H., Tada, M., Takahashi, M., Kashiwazaki, H., Hida, Y., Harnada, J., Asaka, M. and Moriuchi T.: "Dominant negative mutations of the tumor suppressor p53 relating to early onset of glioblastoma multiforme."Cancer Res.. 59. 4765-4769 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamamoto, K., Nakata, D., Tada, M., Tonoki, H., Nishida, T., Hirai, A., Ba, Y., Aoyama, T., Hamada, J., Furuuchi, K., Harada, H., Hirai, K., Shibahara, N., Katsuoka, Y. and Monuchi T.: "A functional and quantitative mutational analysis of p53 mutations in yeast indicates strand biases and different roles of mutations in DMBA- and BBN-induced tumors in rats."Int. J. Cancer. 83. 700-705 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Onodera, M., Ariga, T., Kawamura, N., Kobayashi, I., Ohtsu, M., Yamada, M., Tame, A., Furuta, H., Okano, M., Matsumoto, S., Kotani, H., McGarrity GJ, Blaese RM, Sakiyama Y.: "Successful peripheral T-lymphocyte=directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency."Blood. 91. 30-36 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 細川眞澄男: "Increased E1AF expression in mouse fibrosarcoma promotes metastasis through induction of MT1-MMP expression"Oncogene. 18. 1771-1776 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 守内哲也: "Identification of an autoimmune enteropathy-related 75-kilodalton antigen"Gastroenterology. 117. 823-830 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 守内哲也: "Somatic mutations of the APC gene in primary breast cancers"Am. J. Pathol.. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] 守内哲也: "Dominant negative mutations of the tumor suppressor p53 relating to early onset of glioblastoma multiforme"Cancer Res.. 59. 4765-4769 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 守内哲也: "A functional and quanitative mutational analysis of p53 mutations in yeast indicates strand biases and different roles of mutations in DMBA- and BBN-induced tumors"Int. J. Cancer. 83. 700-705 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 崎山幸雄: "Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency"Blood. 91. 30-36 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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