p53QS -: An old mutant teaches us new tricks

The p53 protein functions as a tumor suppressor, preventing aberrant cellular proliferation in response to various genotoxic and non-genotoxic stress signals. Although p53' s ability to induce apoptosis is critical to its capacity to suppress tumorigenesis, the role of transcriptional activation in p53' s apoptotic function has been highly controversial. To address this issue, our laboratory generated a p53 mutant knock-in mouse strain in which residues 25 and 26, previously shown to be critical for p53' s transactivation function, were mutated from leucine and tryptophan to glutamine and serine, respectively. Our analysis of cells derived from these mice provided significant insight into p53 activity at both the molecular and cellular level. In particular, our data suggest that p53 utilizes discrete mechanisms to transactivate different target genes, and that p53 employs distinct mechanisms to induce apoptosis in response to different stresses. This p53(QS) mutant mouse strain represents a powerful means to dissect p53 function in vivo.