TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting proteins that regulate the transcriptional activity of E2F-1/DP-1.
We report the isolation of TRIP-Br1, a transcriptional regulator that interacts with the PHD-bromodomain of co-repressors of Krueppel-associated box (KRAB)-mediated repression, KRIP-1(TIF1beta) and TIF1alpha, as well as the co-activator/adaptor p300/CBP. TRIP-Br1 and the related protein TRIP-Br2 possess transactivation domains. Like MDM2, which has a homologous transactivation domain, TRIP-Br proteins functionally ... contact DP-1, stimulating E2F-1/DP-1 transcriptional activity. KRIP-1 potentiates TRIP-Br protein co-activation of E2F-1/DP-1. TRIP-Br1 is a component of a multiprotein complex containing E2F-1 and DP-1. Co-expression of the retinoblastoma gene product (RB) abolishes baseline E2F-1/DP-1 transcriptional activity as well as TRIP-Br/KRIP-1 co-activation, both of which are restored by the adenovirus E1A oncoprotein. These features suggest that TRIP-Br proteins function at E2F-responsive promoters to integrate signals provided by PHD- and/or bromodomain- containing transcription factors. TRIP-Br1 is identical to the cyclin-dependent kinase 4 (cdk4)-binding protein p34(SEI-1), which renders the activity of cyclin D/cdk4 resistant to the inhibitory effect of p16(INK4a) during late G(1). TRIP-Br1(p34(SEI-1)) is differentially overexpressed during the G(1) and S phases of the cell cycle, consistent with a dual role for TRIP-Br1(p34(SEI-1)) in the regulation of cell cycle progression through sequential effects on the transcriptional activity of E2F-responsive promoters during G(1) and S phases.
Mesh Terms:
Animals, Carrier Proteins, Cell Cycle Proteins, Cell Line, Conserved Sequence, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Gene Expression, Humans, Kruppel-Like Transcription Factors, Mice, Models, Genetic, Molecular Sequence Data, Multigene Family, Nuclear Proteins, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Repressor Proteins, Retinoblastoma-Binding Protein 1, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factor DP1, Transcription Factors, Transcription, Genetic, Two-Hybrid System Techniques, Zinc Fingers
Animals, Carrier Proteins, Cell Cycle Proteins, Cell Line, Conserved Sequence, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Gene Expression, Humans, Kruppel-Like Transcription Factors, Mice, Models, Genetic, Molecular Sequence Data, Multigene Family, Nuclear Proteins, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Repressor Proteins, Retinoblastoma-Binding Protein 1, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factor DP1, Transcription Factors, Transcription, Genetic, Two-Hybrid System Techniques, Zinc Fingers
EMBO J.
Date: May. 01, 2001
PubMed ID: 11331592
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