Activation of p53 by oncogenes

Lowe, S. W. (March 1999) Activation of p53 by oncogenes. Endocr Relat Cancer, 6 (1). pp. 45-8. ISSN 1351-0088 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/10732786
DOI: 10.1677/erc.0.0060045

Abstract

p53 is activated by a variety of cellular stresses, including DNA damage, hypoxia, and mitogenic oncogenes, but the extent to which each signal engages p53 as a tumour suppressor remains unknown. In non-immortal cells, the adenovirus E1A oncogene activates p53 to promote apoptosis, whereas oncogenic ras activates p53 to promote cellular senescence. Inactivation of p53 prevents E1A-induced apoptosis or Ras-induced senescence, allowing proliferation to continue unabated. In each instance, the ability of the oncogene to activate p53 involves the same functions as are required for their transforming potential, implying that p53 activation acts as a fail-safe mechanism to counter hyperproliferative signals. Furthermore, p19(ARF) is strictly required for oncogene signalling to p53. The fact that ARF--itself a tumour suppressor--acts as an intermediary in this response argues that the tumour suppressor activity of p53 can arise from its ability to eliminate oncogene-expressing cells.

Item Type: Paper
Uncontrolled Keywords: Adenovirus E1A Proteins/ physiology Animals Apoptosis/ physiology Cell Aging/physiology Cell Cycle Genes, Tumor Suppressor Genes, p53 Genes, ras Humans Oncogenes Proteins/ physiology Proto-Oncogene Proteins p21(ras)/ physiology Research Support, U.S. Gov't, P.H.S. Signal Transduction/ genetics Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53/ metabolism
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
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
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein > Ras
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Kathleen Darby
Date: March 1999
Date Deposited: 22 Apr 2014 16:33
Last Modified: 22 Apr 2014 16:33
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29863

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