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 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.
Hsu
S I
SI
Renal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Yang
C M
CM
Sim
K G
KG
Hentschel
D M
DM
O'Leary
E
E
Bonventre
J V
JV
D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015870:Gene Expression; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012097:Repressor Proteins; D056465:Retinoblastoma-Binding Protein 1; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D000076183:Tripartite Motif-Containing Protein 28; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers / Q000502:physiology*; D000092468:Bromodomain Containing Proteins
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D012097:Repressor Proteins; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; D000076183:Tripartite Motif-Containing Protein 28; C533431:Arid4a protein, mouse; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; C402464:SERTAD1 protein, human; C426827:SERTAD2 protein, human; D000092468:Bromodomain Containing Proteins; C485730:Sertad1 protein, mouse; C486065:Sertad2 protein, mouse; C493735:TFDP1 protein, human; C493736:Tfdp1 protein, mouse; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; C103190:Trim28 protein, mouse