CtBPs (C-terminal binding proteins) are highly conserved transcriptional co-repressors involved in various processes such as development, cell cycle regulation and transformation. The negative modulator CtBP was shown to interact with RIP140 through a sequence, PIDLSCK, in the amino-terminal third of the RIP140 protein. RIP140 is acetylated at this Lys residue by CBP/p300 and this modification abolishes the CtBP interaction, resulting in a loss of repression. Acetylation of transcriptional repressors may be a general mode of disrupting CtBP corepressor complexes.