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

  1. Yanhong Shi,
  2. Michael Downes,
  3. Wen Xie,
  4. Hung-Ying Kao2,
  5. Peter Ordentlich1,
  6. Chih-Cheng Tsai,
  7. Michelle Hon, and
  8. Ronald M. Evans3
  1. Howard Hughes Medical Institute, The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA

Abstract

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.

Keywords

Footnotes

  • Present addresses: 1X-Ceptor Therapeutics, Inc., San Diego, CA 92121, USA.

  • 2 Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.

  • 3 Corresponding author.

  • E-MAIL evans{at}salk.edu; FAX (858) 455-1349.

  • Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.871201.

    • Received December 5, 2000.
    • Accepted March 1, 2001.
| Table of Contents

G&D Most Read

View all ...

Life Science Alliance