P53 and mdm-2: interactions between tumor suppressor gene and oncogene products.
The p53 tumor suppressor gene is the most commonly mutated gene in human cancers and, although mutation leads to loss of p53 suppression of cell growth, it can also result in new functions which enhance tumorigenicity. These mutations often lead to loss of p53 transcriptional activation activity, which is likely to account for the loss of growth control. The p53 protein induces expression of the GADD45 and mdm-2 genes, and the respective roles of the products of these two genes in the regulation of growth control, apoptosis, amplification, and the response to DNA damage remain to be determined. Although some facts are clear at this juncture, we can surely expect some surprises in the future, including additional functions for the p53 tumor suppressor gene product and a constant reevaluation of our present concepts. The study of the p53 regulatory pathway, however, should lead us to additional important genes and proteins central to an explanation of the origins of cancer.
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, NJ 08544-1014.
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Levine
D000595:Amino Acid Sequence; D001483:Base Sequence; D004249:DNA Damage; D004252:DNA Mutational Analysis; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D014158:Transcription, Genetic
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2