The p107 tumor suppressor induces stable E2F DNA binding to repress target promoters.
E2F transcription factors are key players in the regulation of proliferation, apoptosis, and differentiation in mammalian cells. E2Fs are negatively regulated by members of the retinoblastoma protein family, Rb, p107 and p130. During adenovirus infection, viral proteins are expressed that displace Rb family members from E2Fs and recruit E2F complexes to viral and cellular promoter regions. This recruitment of E2F involves the induction of stable E2F binding to inverted E2F binding sites in the Ad E2a and cellular E2F-1 promoters and induces both viral and cellular gene expression. The cellular p107 tumor suppressor also displays such regulation of E2F DNA binding activity. p107 induces stable E2F-4/DP binding to inverted E2F binding sites in the Ad E2a and cellular E2F-1 promoters. The induction of E2F DNA binding by p107 minimally requires the sequences in p107 that mediate E2F interaction. The related tumor suppressor, p130, also effects this function. p107 levels increase substantially as cells progress through S phase. p107 induction of E2F DNA binding was observed primarily in S phase cells coincident with the increase in p107 protein levels. The results of promoter activity assays directly correlate the induction of E2F DNA binding by p107 with effective transcriptional repression. These results support a model in which p107 and p130 induce the stable binding of E2F complexes to promoters that drive expression of critical regulatory proteins such as E2F-1. Since p107 and p130 bind histone deacetylase complexes (HDACs) which repress promoter activity, p107-E2F and p130-E2F would stably recruit repressor complexes to effect efficient promoter repression.
O'Connor
R J
RJ
Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York, Stony Brook, New York, NY 11794, USA.
Schaley
J E
JE
Feeney
G
G
Hearing
P
P
D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050704:E2F4 Transcription Factor; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D011506:Proteins; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D016196:S Phase; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors; D004247:DNA