期刊
GENES & DEVELOPMENT
卷 15, 期 9, 页码 1140-1151出版社
COLD SPRING HARBOR LAB PRESS
DOI: 10.1101/gad.871201
关键词
SMRT; HDAC1; SRA; attenuation of hormonal response
资金
- NICHD NIH HHS [HD27183, R01 HD027183] Funding Source: Medline
- NIDDK NIH HHS [R37 DK057978, 9R01DK57978] Funding Source: Medline
A yeast two-hybrid screen using the conserved carboxyl terminus of the nuclear receptor corepressor SMRT as a bait led to the isolation of a novel human gene termed SHARP (SMRT/HDAC1 Associated Repressor Protein). SHARP is a potent transcriptional repressor whose repression domain (RD) interacts directly with SMRT and at least five members of the NuRD complex including HDAC1 and HDAC2. In addition, SHARP binds to the steroid receptor RNA coactivator SRA via an intrinsic RNA binding domain and suppresses SRA-potentiated steroid receptor transcription activity. Accordingly, SHARP has the capacity to modulate both liganded and nonliganded nuclear receptors. Surprisingly, the expression of SHARP is itself steroid inducible, suggesting a simple feedback mechanism for attenuation of the hormonal response.
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