| Project/Area Number |
13470219
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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 |
Endocrinology
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
SARUTA Takao KEIO UNIVERSITY, SCHOOL OF MEDICINE, Professor, 医学部, 教授 (70051571)
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| Co-Investigator(Kenkyū-buntansha) |
KURIHARA Isao KEIO UNIVERSITY, SCHOOL OF MEDICINE, Assistant, 医学部, 助手 (90338038)
SHIBATA Hirotaka KEIO UNIVERSITY, HEALTH CENTER, ASSISTANT PROFESSOR, 保健管理センター, 専任講師 (20245484)
HAYASHI Matsuhiko KEIO UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 教授 (60129608)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Estrogen Receptor / coactivator / COUP-TF / FHL2 / SERM / FHL-2 / COUP-TFI / 転写共役因子 / coactivator / corepressor / 核内受容体 / コリプレッサー |
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| Research Abstract |
1) We screened Estrogen Receptor α (ERα)-interacting proteins using yeast two hybrid system from a human heart cDNA library. We successfully identified LIM-only-domain containing factor FHL2 and Sumoylation enzymes Ubc9 and PIAS1 as ERα-interacting proteins in an estradiol-sensitive manner. FHL2 is highly expressed in cardiac muscle specifically, and reported that it interacts with several transcription factors, such as Androgen Receptor, AP-1, CREB and CREM. This is the first report of FHL2 as ERα interacting protein. FHL2 interacts with ERα in the presence of 17β-estradiol, but there was no significant influence on transcriptional activity through ERα by transient transfection assay using an ERE-E 1b-Luciferase reporter. Given the fact that FHL2 is specifically highly expressed in the cardiac muscle, FHL2 is likely to be involved in the pathophysiology of cardiac hypertrophy.
2) We have previously identified SUMOylation enzymes Ubc9 and PIAS1 as COUP-TFI interacting proteins. In the present project, we also identified them as ERα-interacting proteins. We investigated the role of these proteins in ER-mediated transcription, and found that they function as transcriptional coactivators of ERα. Since a recent report showed that COUP-TFI activates ERα through phospholylation of Ser118 of ERα, it is conceivable that Ubc9, PIAS1 and COUP-TFI form ternary complex to modulate ERα transcriptional activities.
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