The N-terminal transactivation domain of ATF2 is a target for the co-operative activation of the c-jun promoter by p300 and 12S E1A.
The adenovirus E1A proteins activate the c-jun promoter through two Jun/ATF-binding sites, jun1 and jun2. P300, a transcriptional coactivator of several AP1 and ATF transcription factors has been postulated to play a role in this activation. Here, we present evidence that p300 can control c-jun transcription by acting as a cofactor for ATF2: (1) Over-expression of p300 was found to stimulate c-jun transcription both in the presence and absence of E1A. (2) Like E1A, p300 activates the c-jun promoter through the junl and jun2 elements and preferentially activates the N-terminal domain of ATF2. (3) Co-immunoprecipitation assays of crude cell extracts indicate that endogenous p300/CBP(-like) proteins and ATF2 proteins are present in a multiprotein complex that can bind specifically to the jun2 element. We further demonstrate that the Stress-Activated-Protein-Kinase (SAPK) target sites of ATF2, Thr69 and Thr71 are not required for the formation of the p300/CBP-ATF2 multiprotein complex. These data indicate that E1A does not inhibit all transcription activation functions of p300, and, in fact, cooperates with p300 in the activation of the ATF2 N-terminus.
D051698:Activating Transcription Factor 2; D017500:Adenovirus E1A Proteins / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002461:Cell Line, Transformed; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D016758:Genes, jun; D006801:Humans; D046911:Macromolecular Substances; D048291:Mitogen-Activated Protein Kinase 12; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010769:Phosphothreonine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases