Proteasomal regulation of nuclear receptor corepressor-mediated repression

  1. Jinsong Zhang1,
  2. Matthew G. Guenther1,
  3. Richard W. Carthew2, and
  4. Mitchell A. Lazar1,3
  1. 1Departments of Medicine, Genetics, and Biochemistry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 USA; 2Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 USA

Abstract

Repression of gene transcription is a fundamental property of nuclear hormone receptors. We report here that cell-specific repression by nuclear receptors correlates with levels of nuclear receptor corepressor (N-CoR) protein. N-CoR protein levels are regulated by mSiah2, a mammalian homolog of Drosophila Seven in absentiathat targets N-CoR for proteasomal degradation. mSiah2 expression is cell-type specific and differentially regulates the repressive activities of nuclear receptors. These findings establish targeted proteolysis of transcriptional coregulators as a mechanism for cell-specific regulation of gene transcription.

Keywords

Footnotes

  • 3 Corresponding author.

  • E-MAIL lazar{at}mail.med.upenn.edu; FAX (215) 898-5408.

    • Received January 13, 1998.
    • Accepted April 17, 1998.
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