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  • Original Paper
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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

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 jun1 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.

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Acknowledgements

We are grateful to Dr Nic Jones, Dr Kenneth Low, Dr Richard Eckner, Dr Yang Shi and Dr Angel for plasmid constructs, to Dr Eric Kalkhoven for helpful discussions and to Dr Hans van Ormondt for help in preparing the manuscrupt. This work was supported by the Netherlands Organization for Scientific Research (NWO) through the Foundation of Chemical Research in the Netherlands (SON, MD), by a fellowship of the Royal Netherlands Academy of Arts and Sciences (KNAW, HvD) and by a grant from the Dutch Cancer Society (KWF, PS).

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Duyndam, M., van Dam, H., Smits, P. et al. 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. Oncogene 18, 2311–2321 (1999). https://doi.org/10.1038/sj.onc.1202584

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