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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.
- Source :
-
Oncogene [Oncogene] 1999 Dec 16; Vol. 18 (54), pp. 7825-33. - Publication Year :
- 1999
-
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.
- Subjects :
- Adenovirus E1A Proteins genetics
Animals
Cells, Cultured
Fibroblasts
Genes, p53
HeLa Cells
Humans
Kidney
Oncogene Proteins metabolism
Rats
Recombinant Proteins metabolism
Transfection
Adenovirus E1A Proteins metabolism
Cell Transformation, Neoplastic
Gene Expression Regulation
Proliferating Cell Nuclear Antigen genetics
Promoter Regions, Genetic
Transcriptional Activation physiology
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 18
- Issue :
- 54
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 10618724
- Full Text :
- https://doi.org/10.1038/sj.onc.1203294