The recognition that the p53 tumour suppressor gene is frequently inactivated in human cancers has galvanized an intense pursuit of the fundamental mechanisms by which the encoded protein halts malignant transformation and tumour progression. It is now evident that p53 is a multifunctional transcription factor that is intimately involved in the cellular response to stressful stimuli such as DMA damage and hypoxia. In addition to its role in the surveillance mechanisms that arrest cell cycle progression, p53 can also trigger apoptosis in response to DMA damage or oncogenic aberrations that induce aberrant cell cycle progression. Since p53 is a critical component for DMA damage-induced apoptosis, the frequent occurrence of p53 mutations in human neoplasia provides a genetic basis for their poor response to genotoxic anticancer agents. Two recent studies offer key insights into the molecular mechanisms employed by p53 to induce cell death. One model indicates that p53 induces redox-related genes that generate reactive oxygen species and promote the oxidative degradation of mitochondrial components. The other demonstrates p53-mediated induction of DR5, a death receptor of the tumour necrosis factor receptor family, that induces death by caspase-mediated proteolysis. These insights provide an exhilarating array of possible therapeutic interventions against p53-deficient human cancers that may pay enormous dividends in the not-too-distant future.
|Original language||English (US)|
|Number of pages||8|
|State||Published - 1998|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology