The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase.
The transcription factor E2F plays a major role in cell cycle control in mammalian cells. E2F binding sites, which are present in the promoters of a variety of genes required for S phase, shift from a negative to a positive role in transcription at the commitment point, a crucial point ... in G1 that precedes the G1/S transition. Before the commitment point, E2F activity is repressed by members of the pocket proteins family. This repression is believed to be crucial for the proper control of cell growth. We have previously shown that Rb, the founding member of the pocket proteins family, represses E2F1 activity by recruiting the histone deacetylase HDAC1. Here, we show that the two other members of the pocket proteins family, p107 and p130, also are able to interact physically with HDAC1 in live cells. HDAC1 interacts with p107 and Rb through an "LXCXE"-like motif, similar to that used by viral transforming proteins to bind and inactivate pocket proteins. Indeed, we find that the viral transforming protein E1A competes with HDAC1 for p107 interaction. We also demonstrate that p107 is able to interact simultaneously with HDAC1 and E2F4, suggesting a model in which p107 recruits HDAC1 to repress E2F sites. Indeed, we demonstrate that histone deacetylase activity is involved in the p107- or p130-induced repression of E2F4. Taken together, our data suggest that all members of the E2F family are regulated in early G1 by similar complexes, containing a pocket protein and the histone deacetylase HDAC1.
Mesh Terms:
Carrier Proteins, Cell Cycle Proteins, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, E2F4 Transcription Factor, Histone Deacetylases, Humans, Jurkat Cells, Nuclear Proteins, Phosphoproteins, Phosphorylation, Protein Binding, Proteins, Retinoblastoma-Binding Protein 1, Retinoblastoma-Like Protein p107, Retinoblastoma-Like Protein p130, Transcription Factor DP1, Transcription Factors, Transcription, Genetic
Carrier Proteins, Cell Cycle Proteins, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, E2F4 Transcription Factor, Histone Deacetylases, Humans, Jurkat Cells, Nuclear Proteins, Phosphoproteins, Phosphorylation, Protein Binding, Proteins, Retinoblastoma-Binding Protein 1, Retinoblastoma-Like Protein p107, Retinoblastoma-Like Protein p130, Transcription Factor DP1, Transcription Factors, Transcription, Genetic
Proc. Natl. Acad. Sci. U.S.A.
Date: Sep. 01, 1998
PubMed ID: 9724731
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