1999 Fiscal Year Final Research Report Summary
Molecular analysis of novel PDZ domain-containing gene encoding autoantigen of autoimmune enteropathy
| Project/Area Number |
10670698
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
HOSOKAWA Masuo Hokkaido University, School of Medicine, Professor, 医学部, 教授 (20001901)
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| 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)
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| Project Period (FY) |
1998 – 1999
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| Keywords | enteropathy / AIE-75 / PDZ domain / yeast / Wnt pathway / MCC |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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).
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
