Mechanism of corepressor binding and release from nuclear hormone receptors

Laszlo Nagy, Hung Ying Kao, James D. Love, Chuan Li, Ester Banayo, John T. Gooch, V. Krishna, K. Chatterjee, Ronald M. Evans, John W.R. Schwabe

Research output: Contribution to journalArticle

Abstract

The association of transcription corepressors SMRT and N-CoR with retinoid and thyroid receptors results in suppression of basal transcriptional activity. A key event in nuclear receptor signaling is the hormone-dependent release of corepressor and the recruitment of coactivator. Biochemical and structural studies have identified a universal motif in coactivator proteins that mediates association with receptor LBDs. We report here the identity of complementary acting signature motifs in SMRT and N- CoR that are sufficient for receptor binding and ligand-induced release. Interestingly, the motif contains a hydrophobic core (ΦxxΦΦ) similar to that found in NR coactivators. Surprisingly, mutations in the amino acids that directly participate in coactivator binding disrupt the corepressor association. These results indicate a direct mechanistic link between activation and repression via competition for a common or at least partially overlapping binding site.

Original languageEnglish (US)
Pages (from-to)3209-3216
Number of pages8
JournalGenes and Development
Volume13
Issue number24
DOIs
Publication statusPublished - Dec 15 1999
Externally publishedYes

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Keywords

  • Coactivator binding
  • Corepressor binding
  • Nuclear hormone receptors
  • SMRT
  • Transcription corepressors

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Nagy, L., Kao, H. Y., Love, J. D., Li, C., Banayo, E., Gooch, J. T., ... Schwabe, J. W. R. (1999). Mechanism of corepressor binding and release from nuclear hormone receptors. Genes and Development, 13(24), 3209-3216. https://doi.org/10.1101/gad.13.24.3209