| First Author | Melis JP | Year | 2011 |
| Journal | Oncogene | Volume | 30 |
| Issue | 15 | Pages | 1764-72 |
| PubMed ID | 21151170 | Mgi Jnum | J:170769 |
| Mgi Id | MGI:4947328 | Doi | 10.1038/onc.2010.552 |
| Citation | Melis JP, et al. (2011) Genotoxic exposure: novel cause of selection for a functional DeltaN-p53 isoform. Oncogene 30(15):1764-72 |
| abstractText | 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 DeltaN-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 DeltaN-p53 accounts, at least in mice, for a cancer phenotype. We also show that gene expression profiles of embryonic stem (ES) cells carrying the DeltaN-p53 isoform in a p53-null background are divergent from p53 knockout ES cells, and therefore postulate that DeltaN-p53 itself has functional transcriptional properties. |
