| Project/Area Number |
13671201
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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 |
Metabolomics
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
OGATA Makiko TWMU, Diabetes Center, Assistant of professor, 医学部, 助手 (10233404)
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| Co-Investigator(Kenkyū-buntansha) |
IWASAKI Naoko TWMU, Diabetes Center, Lecturer, 医学部, 講師 (70203370)
AWAJI Takeo TWMU, Department of Physiology, Lecturer, 医学部, 講師 (60297546)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | Diabetes Mellitus / MODY / HNF4α / HNF4 α / HNF4α / SHP |
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| Research Abstract |
Mutations in small heterodimer partner (SHP) and hepatocyte nuclear factor 4α (HNF4α) are associated with mild obesity and diabetes mellitus, respectively. SHP and HNF4α appear to function together to determine normal pancreatic β-cell function. We examined the subcellular localization and interaction of SHP and HNF4α in living cells by tagging them with yellow and cyan variants of green fluorescent protein (GFP). The results showed that SHP resided only in the cytoplasm in COS-7 cells whereas it was localized predominantly in the nucleus in MIN6 cells. In contrast, HNF4α was localized in the nuclei of both cell types. Co-expression of SHP and HNF4α in COS-7 cells led to localization of SHP into the nucleus, the extent of which depended on the amount of HNF4α. Fluorescence resonance energy transfer between GFP-tagged SHP and HNF4α in living COS-7 cells indicating a specific association of SHP with HNF4α in the nucleus. The results suggest that SHP normally resides in the cytoplasm and is translocated into the nucleus on interacting with a nuclear receptor partner such as HNF4α.
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