Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Carrier Proteins*
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Cell Cycle Proteins*
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Cell Line
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Conserved Sequence
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DNA-Binding Proteins / genetics
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E2F Transcription Factors
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E2F1 Transcription Factor
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Gene Expression
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Humans
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors
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Mice
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Models, Genetic
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Molecular Sequence Data
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Multigene Family / genetics
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Nuclear Proteins / metabolism
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Protein Structure, Tertiary / physiology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-mdm2
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Repressor Proteins*
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Retinoblastoma-Binding Protein 1
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Sequence Homology, Amino Acid
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factor DP1
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / physiology*
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Tripartite Motif-Containing Protein 28
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Two-Hybrid System Techniques
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Zinc Fingers / physiology*
Substances
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Arid4a protein, mouse
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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E2F Transcription Factors
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E2F1 Transcription Factor
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E2F1 protein, human
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E2f1 protein, mouse
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors
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Nuclear Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Retinoblastoma-Binding Protein 1
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SERTAD1 protein, human
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SERTAD2 protein, human
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Sertad1 protein, mouse
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Sertad2 protein, mouse
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TFDP1 protein, human
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Tfdp1 protein, mouse
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Trans-Activators
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Transcription Factor DP1
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Transcription Factors
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MDM2 protein, human
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Mdm2 protein, mouse
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Proto-Oncogene Proteins c-mdm2
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Trim28 protein, mouse
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Tripartite Motif-Containing Protein 28
Associated data
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GENBANK/AF366400
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GENBANK/AF366401
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GENBANK/AF366402
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GENBANK/AF366403