| Project/Area Number |
14370179
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
HIGASHITSUJI Hiroaki Kyoto University, Faculty of Medicine, Department of Clinical Molecular Biology, associate professor, 医学研究科, 助手 (60281094)
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Jun Kyoto University, Department of Clinical Molecular Biology, Professor, 医学研究科, 教授 (50173430)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | proteasome / tumor suppressor / hepatocellular carcinoma / ユビキチン / 26Sプロテアソーム / トランスジェニックマウス / がん遺伝子 |
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| Research Abstract |
Gankyrin is overexpressed in human hepatocellular carcinomas. Its overexpression leads to transformation of MH-3T3 cells and induces tumor formation in nude mice. Ite overexpression correlates with hyperphosphorylation and degradation of pRB protein. Gankyrin has been shown to bind to cyclin D-dependent kinase 4, one of whose substrates is pRB. Gankyrin has also been found in yeast two-hybrid screens to form a complex with the human S6b ATPase subunit of the 19S regulatory complex of the 26S proteasome. The other protein shown to interact with gankyrin is a melanoma antigen MACE-A4. Thin interaction suppresses the oncogenic activity of gankyrin. Gankyrin expression was shown to increase during liver regeneration after hepatic resection or fuluminant hepatitis. MAGE-A4 was processed to generate a C-terminal fragment of 104 amino acids, and induced p53-dependent or independent apoptosis in tumour cells. Gankyrin overexpression functions as a E3 cofactors and leads to protein degradation of the tumour suppressors. We constructed a gankyrin-transgenic mouse, using HBV-derived promoter and enhances These mice expressed low levels of gankyrin protein in the livers. However, it is shown that they have tumors in the livers.
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