A mechanism for Rb/p130-mediated transcription repression involving recruitment of the CtBP corepressor

Previous work has demonstrated the critical role for transcription repressi on in quiescent cells through the action of E2F-Rb or E2F-p130 complexes, R ecent studies have shown that at least one mechanism for this repression in volves the recruitment of histone deacetylase, Nevertheless, these studies also suggest that other events likely contribute to EZF/Rb-mediated repress ion. Using a yeast two-hybrid screen to identify proteins that specifically interact with the Rb-related p130 protein, we demonstrate that p130, as we ll as Rb, interacts with a protein known as CtIP, This interaction depends on the p130 pocket domain, which is important for repression activity, as w ell as an LXCXE sequence within CtIP, a motif previously shown to mediate i nteractions of viral proteins with Rb, CtIP interacts with CtBP, a protein named for its ability to interact with the C-terminal sequences of adenovir us EIA, Recent work has demonstrated that the Drosophila homologue of CtBP is a transcriptional corepressor for Hairy, Knirps, and Snail. We now show that both CtIP and CtBP can efficiently repress transcription when recruite d to a promoter by the Ga14 DNA binding domain, thereby identifying them as corepressor proteins. rc Moreover, the full repression activity of CtIP re quires a PLDLS domain that is also necessary for the interaction with CtBP. We propose that E2F-mediated repression involves at least two events, eith er the recruitment of a histone deacetylase or the recruitment of the CtIP/ CtBP corepressor complex.