Complementary functions of E1a conserved region 1 cooperate with conserved region 3 to activate adenovirus serotype 5 early promoters.
The amino-terminal region of the adenovirus type 5 E1a protein including conserved regions (CRs) 1 and 2 binds the 105-kDa retinoblastoma protein and a second, 300-kDa, cellular protein. We show that mutant viruses with deletions of CR1 which release the binding of either p105 or p300 still activate early promoters and infect cells productively. However, mutations which disrupt binding of both proteins disrupt early promoter activity and block the viral life cycle. Ela CR3, which has an established role in early promoter activation, can act in trans to the amino-terminal functions. This suggests that the amino terminus provides distinct, redundant functions related to p300 and Rb binding that synergize with CR3 to transactivate early genes.
Howard Hughes Medical Institute, Department of Biochemistry, New York University Medical Center, New York 10016.
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D016475:3T3 Cells; D000256:Adenoviridae / Q000145:classification / Q000235:genetics* / Q000254:growth & development; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D004171:Diploidy; D050881:E1A-Associated p300 Protein; D005347:Fibroblasts / Q000166:cytology; D015967:Gene Expression Regulation, Viral; D005816:Genetic Complementation Test; D006801:Humans; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D012703:Serotyping; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014779:Virus Replication
D017500:Adenovirus E1A Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse