We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Genotoxic exposure: novel cause of selection for a functional ΔN-p53 isoform.
- Authors
Melis, J P M; Hoogervorst, E M; van Oostrom, C T M; Zwart, E; Breit, T M; Pennings, J L A; de Vries, A; van Steeg, H
- Abstract
The p53 gene is frequently mutated in cancers and it is vital for cell cycle control, homeostasis and carcinogenesis. We describe a novel p53 mutational spectrum, different to those generally observed in human and murine tumors. Our study shows a high prevalence of nonsense mutations in the p53 N terminus of 2-acetylaminofluorene (2-AAF)-induced urinary bladder tumors. These nonsense mutations forced downstream translation initiation at codon 41 of Trp53, resulting in the aberrant expression of the p53 isoform ΔN-p53 (or p44). We propose a novel mechanism for the origination and the selection for this isoform. We show that chemical exposure can act as a novel cause of selection for this truncated protein. In addition, our data suggest that the occurrence of ΔN-p53 accounts, at least in mice, for a cancer phenotype. We also show that gene expression profiles of embryonic stem (ES) cells carrying the ΔN-p53 isoform in a p53-null background are divergent from p53 knockout ES cells, and therefore postulate that ΔN-p53 itself has functional transcriptional properties.
- Subjects
GENETIC toxicology; CARCINOGENESIS; CANCER cells; GENE expression; EMBRYONIC stem cells; BIOLOGICAL divergence; GENETIC mutation; LABORATORY mice
- Publication
Oncogene, 2011, Vol 30, Issue 15, p1764
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2010.552