Sharp, an inducible cofactor that integrates nuclear receptor repression and activation

Yanhong Shi, Michael Downes, Wen Xie, Hung Ying Kao, Peter Ordentlich, Chih Cheng Tsai, Michelle Hon, Ronald M. Evans

Research output: Contribution to journalArticlepeer-review

265 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1140-1151
Number of pages12
JournalGenes and Development
Issue number9
Publication statusPublished - 2001 May 1

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology


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