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

• Project/Area Number: 10670698
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: HOKKAIDO 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: ¥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)
• Keywords: enteropathy / 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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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)
• [Publications] 守内哲也: "Identification of an autoimmune enteropathy-related 75-kilodalton antigen"Gastroenterology. 117. 823-830 (1999)
• [Publications] 守内哲也: "Somatic mutations of the APC gene in primary breast cancers"Am. J. Pathol.. (印刷中).
• [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)
• [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)
• [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)