Heterodimerization of the transcription factors E2F-1 and DP-1 is required for binding to the adenovirus E4 (ORF6/7) protein.
Adenovirus infection leads to E1A-dependent activation of the transcription factor E2F. E2F has recently been identified in complexes with cellular proteins such as the retinoblastoma protein (pRB) and the two pRB family members p107 and p130. E1A dissociates E2F from these cellular proteins, and another viral protein, E4 (ORF6/7), can bind to E2F. The binding of E4 to E2F induces the formation of a stable DNA-binding complex containing the two proteins, and stimulation of the adenovirus E2 early promoter can occur. Recent studies have shown that E2F is the combined activity of several proteins, and we demonstrate here that heterodimerization of two of these proteins, E2F-1 and DP-1, is required for stable binding to E4. This complex is formed independently of DNA binding and requires the C-terminal 20 amino acids of E4. Furthermore, the binding is dependent on a region of E2F-1 between amino acids 284 and 358. This region of E2F-1 is conserved in E2F-2 and E2F-3, and deletion of this region drastically reduces the transcriptional activity of the molecule without affecting DP-1 binding, suggesting that this region of the E2F transcription factors is involved in regulating their activity. Our experiments also demonstrate that pRB binding to the E2F-1/DP-1 heterodimer prevents the formation of an E2F-1/DP-1/E4 complex.
Massachusetts General Hospital Cancer Center, Charlestown 02129.
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Harlow
D017504:Adenovirus E4 Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017504:Adenovirus E4 Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D050699:E2F3 Transcription Factor; D056465:Retinoblastoma-Binding Protein 1; C493735:TFDP1 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors