Mechanism of corepressor binding and release from nuclear hormone receptors.

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 (PhixxPhiPhi) 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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Nagy L,Kao HY,Love JD,Li C,Banayo E,Gooch JT,Krishna V,Chatterjee K,Evans RM,Schwabe JW

doi

10.1101/gad.13.24.3209

subject

Has Abstract

pub_date

1999-12-15 00:00:00

pages

3209-16

issue

24

eissn

0890-9369

issn

1549-5477

journal_volume

13

pub_type

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