Receptor-interacting protein 140 (RIP140) has been shown to modulate gene expression directed by a variety of transcription factors from the nuclear receptor superfamily. Nine copies of the “LXXLL” receptor-interacting motif and a recently identified novel ligand-dependent receptor-interacting motif in the carboxyl terminus of the protein direct binding of RIP140 to nuclear receptors. The effect of RIP140 on gene expression depends on its ability to interact with a variety of nuclear factors involved in transcription. In most cases, RIP140 acts as a negative coregulator causing a suppression of transcription. This negative regulation is attributed to its ability to recruit histone deacetylases (HDACs) to transcription factor-occupied promoters. This review discusses recent studies addressing the biological activity of RIP140 as a ligand-dependent negative coregulator for nuclear receptors.
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