The Mechanism of E2F/P130 Mediated Repression and Its Potential Tumor Suppressor Function in Breast Cancer

Abstract : Transcription repression of E2F target genes has been shown to be critical for the maintenance of cellular quiescence and growth control. While it is clear that E2F-Rb and E2F-pl3O complexes promote this transcriptional regulation, the mechanism of action of these complexes remains unclear. The work supported by this grant aims to elucidate the mechanisms of transcriptional repression through E2F-pl3O complexes. Previous results indicated that while repression through pl3O involves recruitment of histone deacetylase, other mechanisms that are histone deacetylase independent are also involved. We have found that pl3O can recruit the CtBP co-repressor protein through interaction with the CtIP protein. We have mapped the domain of CtBP that is important for its co-repressor function (PID domain) and data suggest that CtBP functions as a repressor in part by inactivating the histone acetyltransferase activity of the transcription co-activator, CBP.