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Dual action of the adenovirus E1A 243R oncoprotein on the human proliferating cell nuclear antigen promoter: repression of transcriptional activation by p53

Oncogene volume 18, pages 7825–7833 (1999)Cite this article

Abstract

The promoter of the human proliferating cell nuclear antigen (PCNA) gene is activated by the adenovirus oncoprotein E1A 243R in HeLa cells. To understand the effect of this oncoprotein on PCNA expression in cells that are sensitive to oncogenic transformation by adenovirus, we studied the effect of E1A 243R on PCNA promoter-directed reporter gene expression in cloned rat embryo fibroblast (CREF) and primary baby rat kidney cells. In contrast to the results obtained in HeLa cells, E1A repressed the PCNA promoter in both cell-types. Promoter analysis identified a p53-responsive element that mediates E1A-induced repression. Repression required the intact N-terminus of E1A 243R, as shown by the ability of mutant E1A proteins to repress the promoter, and correlated with the p300-binding region of E1A. The adenovirus E1B 19K protein relieved repression by E1A 243R. These results reveal dual pathways for induction of this essential DNA replication factor and suggest a mechanism for oncogenic cooperativity between the E1A and E1B oncoproteins.

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Acknowledgements

This work was supported by NIH grant CA 13106.

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Authors and Affiliations

  1. Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York, 11724, NY, USA

    Chitra Kannabiran, Gilbert F Morris & Michael B Mathews

  2. Department of Biochemistry and Molecular Biology, New Jersey Medical School, UMDNJ, 185 South Orange Avenue, Newark, 07103-2714, New Jersey, NJ, USA

    Michael B Mathews

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  1. Chitra Kannabiran
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Kannabiran, C., Morris, G. & Mathews, M. Dual action of the adenovirus E1A 243R oncoprotein on the human proliferating cell nuclear antigen promoter: repression of transcriptional activation by p53. Oncogene 18, 7825–7833 (1999). https://doi.org/10.1038/sj.onc.1203294

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