Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 2
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Adenovirus E1A Proteins / physiology*
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Animals
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Binding Sites
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Calcium-Calmodulin-Dependent Protein Kinases / physiology
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Cell Line, Transformed
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Gene Expression Regulation, Viral*
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Genes, jun*
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Humans
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Macromolecular Substances
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Mitogen-Activated Protein Kinase 12
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Mitogen-Activated Protein Kinase 9
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Mitogen-Activated Protein Kinases*
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Multiprotein Complexes
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Phosphothreonine / metabolism
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Promoter Regions, Genetic*
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Protein Kinases / physiology
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Protein Processing, Post-Translational
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Recombinant Fusion Proteins / physiology
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Regulatory Sequences, Nucleic Acid
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Trans-Activators / genetics
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Trans-Activators / physiology*
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Transcription Factors / metabolism*
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Transcriptional Activation*
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p38 Mitogen-Activated Protein Kinases
Substances
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ATF2 protein, human
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Activating Transcription Factor 2
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Adenovirus E1A Proteins
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Cyclic AMP Response Element-Binding Protein
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Macromolecular Substances
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Multiprotein Complexes
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Nuclear Proteins
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Recombinant Fusion Proteins
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Trans-Activators
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Transcription Factors
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Phosphothreonine
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Protein Kinases
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Mitogen-Activated Protein Kinase 12
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Mitogen-Activated Protein Kinase 9
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases