title: The CR1 and CR3 domains of the adenovirus type 5 E1A proteins can independently mediate activation of ATF-2.
abstract: The adenovirus 12S E1A protein can stimulate the activity of the c-jun promoter through a conserved region 1 (CR1)-dependent mechanism. The effect is mediated by two AP-1/ATF-like elements, jun1 and jun2, that preferentially bind c-Jun-ATF-2 heterodimers. In this study, we show that the ATF-2 component of the c-Jun-ATF-2 heterodimer is the primary target for 12S E1A: 12S E1A can enhance the transactivating activity of the N terminus of ATF-2 when fused to a heterologous DNA-binding domain, whereas the transactivating activity of the c-Jun N terminus is not significantly affected. Activation of the ATF-2 N terminus by 12S E1A is dependent on CR1. In the context of the 13S E1A protein, CR1 and CR3 can both contribute to activation of ATF-2, and their relative contributions are dependent on the cell type. In contrast to activation of ATF-2 by stress-inducing agents, CR1-dependent activation of ATF-2 was found not to depend strictly on the presence of threonines 69 and 71 in the N terminus of ATF-2, which are targets for phosphorylation by stress-activated protein kinases (SAPKs). In agreement with this observation, we did not observe phosphorylation of threonines 69 and 71 or constitutively enhanced SAPK activity in E1A- plus E1B-transformed cell lines. These data suggest that CR1-dependent activation of ATF-2 by 12S E1A does not require phosphorylation of threonines 69 and 71 by SAPK.
authors.affiliation: Laboratory for Molecular Carcinogenesis, Sylvius Laboratory, Leiden University, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Duyndam
authors.forename: H
authors.initials: H
authors.lastname: van Dam
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Eb
authors.forename: A
authors.initials: A
authors.lastname: Zantema
mesh_terms: D051698:Activating Transcription Factor 2; D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D017124:Conserved Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D016758:Genes, jun; D006367:HeLa Cells; D006801:Humans; D016350:Leucine Zippers; D008156:Luciferases / Q000096:biosynthesis; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D013912:Threonine; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017500:Adenovirus E1A Proteins; C497107:Atf2 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D013912:Threonine; D008156:Luciferases; D011494:Protein Kinases