A mechanism for Rb/p130-mediated transcription repression involving recruitment of the CtBP corepressor.
Previous work has demonstrated the critical role for transcription repression in quiescent cells through the action of E2F-Rb or E2F-p130 complexes. Recent studies have shown that at least one mechanism for this repression involves the recruitment of histone deacetylase. Nevertheless, these studies also suggest that other events likely contribute to E2F/Rb-mediated repression. Using a yeast two-hybrid screen to identify proteins that specifically interact with the Rb-related p130 protein, we demonstrate that p130, as well as Rb, interacts with a protein known as CtIP. This interaction depends on the p130 pocket domain, which is important for repression activity, as well as an LXCXE sequence within CtIP, a motif previously shown to mediate interactions of viral proteins with Rb. CtIP interacts with CtBP, a protein named for its ability to interact with the C-terminal sequences of adenovirus E1A. 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 recruited to a promoter by the Gal4 DNA binding domain, thereby identifying them as corepressor proteins. Moreover, the full repression activity of CtIP requires a PLDLS domain that is also necessary for the interaction with CtBP. We propose that E2F-mediated repression involves at least two events, either the recruitment of a histone deacetylase or the recruitment of the CtIP/CtBP corepressor complex.
Meloni
A R
AR
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Smith
E J
EJ
Nevins
J R
JR
D000429:Alcohol Oxidoreductases; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D008667:Metalloproteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011506:Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D050717:Retinoblastoma-Like Protein p130; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D008667:Metalloproteins; D010750:Phosphoproteins; D011506:Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D006655:Histone Deacetylases