Molecular mechanism for the nuclear receptor degradation
| Project/Area Number |
15380067
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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 |
Applied biochemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
YANAGISAWA Junn University of Tsukuba, Graduate School of Life and Environmental Sciences, Professor, 大学院・生命環境科学研究科, 教授 (50301114)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2004: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2003: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | estrogen / ERα / nuclear receptor / transcription / ubiqutination / proteasome / protein degradation / 分解 |
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| Research Abstract |
Recent evidence indicates that the transactivation of estrogen receptor α (ERα) requires estrogen-dependent receptor ubiquitination and degradation. Here we show that estrogen-unbound (unliganded) ERα is also ubiquitinated and degraded through an ubiquitin-proteasome pathway. To investigate this ubiquitin-proteasome pathway, we purified the ubiquitin ligase complex for unliganded ERα and identified a protein complex containing the carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP preferentially bound to misfolded ERα and ubiquitinated it to induce degradation. Ligand binding to the receptor induced the dissociation of CHIP from ERα. In CHIP-/-cells, the degradation of unliganded ERα was abrogated, however, estrogen-induced degradation was observed to the same extent as in CHIP+/+ cells. Our findings suggest that ERα is regulated by two independent ubiquitin-proteasome pathways, which are switched by ligand binding to ERα. One pathway is necessary for the transactivation of the receptor and the other is involved in the quality control of the receptor.
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Report
(3 results)
Research Products
(20 results)
