title: Adenovirus E1A activates cyclin A gene transcription in the absence of growth factors through interaction with p107.
abstract: Using the infection of quiescent human fibroblasts with adenovirus type 5 and various deletion mutants, we show that E1A can stimulate transcription of the cyclin A gene in the absence of exogenous growth factors. Required for this activity is conserved region 2 (CR2), while both the N-terminal part of E1A and CR1 are dispensable. This indicates that activation of cyclin A gene expression requires the binding of E1A to p107, while binding to either pRB or p300 is not involved in transcriptional activation. We demonstrate that p107 represses the cyclin A promoter through its cell cycle-regulatory E2F binding site and that 12S E1A can activate the cyclin A promoter, essentially by counteracting its repression by p107. Since Cr2 is required for cell transformation, transcriptional activation of the cyclin A gene by E1A appears to be important for its capacity to override control of cellular growth.
authors.affiliation: Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Zerfass
authors.forename: D
authors.initials: D
authors.lastname: Spitkovsky
authors.forename: A
authors.initials: A
authors.lastname: Schulze
authors.forename: S
authors.initials: S
authors.lastname: Joswig
authors.forename: B
authors.initials: B
authors.lastname: Henglein
authors.forename: P
authors.initials: P
authors.lastname: Jansen-Dürr
mesh_terms: D016475:3T3 Cells; D000260:Adenoviruses, Human / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D016213:Cyclins / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D050720:Retinoblastoma-Like Protein p107; D015533:Transcriptional Activation
chemical_list: D016213:Cyclins; D009687:Nuclear Proteins; C493844:RBL1 protein, human; D012333:RNA, Messenger; C489485:Rbl1 protein, mouse; D050720:Retinoblastoma-Like Protein p107