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

Kannabiran, C., Morris, G. F., Mathews, M. B. (December 1999) Dual action of the adenovirus E1A 243R oncoprotein on the human proliferating cell nuclear antigen promoter: repression of transcriptional activation by p53. Oncogene, 18 (54). pp. 7825-33. ISSN 0950-9232 (Print)

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.

Item Type: Paper
Uncontrolled Keywords: Adenovirus E1A Proteins/genetics/ metabolism Animals Cell Transformation, Neoplastic Cells, Cultured Fibroblasts Gene Expression Regulation Genes, p53 Hela Cells Humans Kidney Oncogene Proteins/metabolism Proliferating Cell Nuclear Antigen/ genetics Promoter Regions (Genetics) Rats Recombinant Proteins/metabolism Research Support, U.S. Gov't, P.H.S. Trans-Activation (Genetics)/ physiology Transfection Tumor Suppressor Protein p53/ metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > E1A protein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
CSHL Authors:
Communities: CSHL labs
Depositing User: Kathleen Darby
Date: 16 December 1999
Date Deposited: 23 Apr 2014 13:34
Last Modified: 30 Apr 2014 17:08
Related URLs:
URI: https://repository.cshl.edu/id/eprint/29858

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