2003 Fiscal Year Final Research Report Summary
Functional Analysis of a novel coactivating cofactor of thyroid hormone receptor, TBP-1
| Project/Area Number |
14571059
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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 |
Endocrinology
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| Research Institution | Gunma University |
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Principal Investigator |
SATOH Teturou Gunma University Graduate School of Medicine, Department of Medicine and Molecular Science, assistant professor, 医学部, 助手 (40302484)
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| Project Period (FY) |
2002 – 2003
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| Keywords | thyroid hormone receptor / Tat binding protein-1 / TBP-1 interacting protein / androgen receptor / Proteasome / transcription cofactor / proteasome inhibitor |
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| Research Abstract |
Using a yeast two-hybrid system, we have isolated and characterized a novel transcriptional cofactor of thyroid hormone receptor (TR) that was identical to Tat-binding protein-1 (TBP-1) originally isolated as a factor interacting with human immunodeficiency virus type I Tat transactivator. TBP-1 has subsequently been identified as a component of the 19S regulatory subunit of 26S proteasome. In this project, we further evaluated the function of TBP-1 and a TBP-1 interacting protein-1 (TBPIP) as transcriptional cofactors of nuclear receptors (NR). The TBP-1 mRNA was ubiquitously expressed in human tissues, whereas TBPIP gene expression was highly restricted in testis. Both TBP-1 and TBPIP could enhance AR-mediated gene activation and synergistically functioned in transient transfection assays. In in vitro binding assays, TBP-1 and TBPIP could directly interact with AR. The TBPIP interaction domain was mapped to the N-terminal coiled-coil region of TBP-1. Several recent studies emphasized the importance of 26S proteasomal system in transactivation function of NR such as estrogen receptor and AR. To investigate whether proteasomal function of TBP-1 and TBPIP was required for TR and AR-mediated gene activation, effects of a proteasome inhibitor, MG132 was evaluated. MG132 significantly inhibit TBP-1 and TBPIP-mediated enhancement of transactivation by TR and AR.
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