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 language | English (US) |
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Pages (from-to) | 3209-3216 |
Number of pages | 8 |
Journal | Genes and Development |
Volume | 13 |
Issue number | 24 |
DOIs | |
State | Published - Dec 15 1999 |
Externally published | Yes |
Keywords
- Coactivator binding
- Corepressor binding
- Nuclear hormone receptors
- SMRT
- Transcription corepressors
ASJC Scopus subject areas
- Genetics
- Developmental Biology