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. 2001 May 1;20(9):2273-85. doi: 10.1093/emboj/20.9.2273.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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 Factor 4
  • 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*
  • Tripartite Motif-Containing Protein 28
  • Two-Hybrid System Techniques
  • Zinc Fingers / physiology*

Substances

  • Arid4a protein, mouse
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Retinoblastoma-Binding Protein 1
  • SERTAD1 protein, human
  • SERTAD2 protein, human
  • Sertad1 protein, mouse
  • Sertad2 protein, mouse
  • TFDP1 protein, human
  • Tfdp1 protein, mouse
  • Trans-Activators
  • Transcription Factor DP1
  • Transcription Factors
  • MDM2 protein, human
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2
  • Trim28 protein, mouse
  • Tripartite Motif-Containing Protein 28

Associated data

  • GENBANK/AF366400
  • GENBANK/AF366401
  • GENBANK/AF366402
  • GENBANK/AF366403