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Hsu, SI, Yang, CM, Sim, KG, Hentschel, DM, O'Leary, E and Bonventre, JV (2001) TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting proteins that regulate the transcriptional activity of E2F-1/DP-1. EMBO J. 20:2273-85
We report the isolation of TRIP-Br1, a transcriptional regulator that interacts with the PHD-bromodomain of co-repressors of Krüppel-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.
Animals; Carrier Proteins; Cell Cycle Proteins; Cell Line; Conserved Sequence; DNA-Binding Proteins/genetics; E2F Transcription Factors; E2F1 Transcription Factor; Gene Expression; Humans; Kruppel-Like Transcription Factors; Mice; Models, Genetic; Molecular Sequence Data; Multigene Family/genetics; Nuclear Proteins/metabolism; Protein Structure, Tertiary/physiology; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins c-mdm2; Repressor Proteins; Retinoblastoma-Binding Protein 1; Sequence Homology, Amino Acid; Trans-Activators/genetics; Trans-Activators/metabolism; Transcription Factor DP1; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic/physiology; Two-Hybrid System Techniques; Zinc Fingers/physiology