CECAD Microsite


The prominent tumor suppressor gene TP53 encodes for a transcription factor that is activated in response to genotoxic stress. Once activated, p53 acts transactivates numerous effector genes, which can be classified into pro-apoptotic (e.g. PUMA, BAX, BAK) and cell cycle-arresting (CDKN1A, RPRM, GADD45A) genes. Our lab could recently show that upstream kinases, such as ATM or the p38MAPK/MK2 complex dictate the quality of the p53 response by selectively promoting or repressing the expression of pro-apoptotic or cell cycle-arresting p53   target genes. To further interrogate the dichotomy of the p53 response, we have used BAC transgenics to generate reporter mice, in which we have fused a BAC-encoded PUMA gene to GFP and a BAC-encoded CDKN1A to tdTomato. These transgenic mice, which express a p53-regulated extra copy of PUMA and/or CDKN1A are viable and fertile. We are currently pursuing both in vitro and in vivo experiments with these reporter animals to characterize mechanisms that regulate the functional outcome of p53 signaling.