Tissue specificity and spatio-temporal dynamics of the p53 transcriptional program.

Transcription factors regulate hundreds of genes and p53 is no exception. As a stress responsive protein, p53 transactivates an array of downstream targets which define its role in maintaining physiological functions of cells/tissues. Despite decades of studies, our understanding of the p53 in vivo transcriptional program is still incomplete. Here we discuss some of the physiological stressors that activate p53, the pathological and physiological implications of p53 activation and the molecular profiling of the p53 transcriptional program in maintaining tissue homeostasis. We argue that the p53 transcriptional program is spatiotemporally regulated in a tissue-specific manner and define a p53 target signature that faithfully depicts p53 activity. We further emphasize that additional in vivo studies are needed to refine the p53 transactivation profile to harness it for therapeutic purposes.