Of the many cellular responses activated by TP53, which ones are critical for tumour suppression?

The tumour suppressor TP53 is a master regulator of several cellular processes that collectively suppress tumorigenesis. The TP53 gene is mutated in similar to 50% of human cancers and these defects usually confer poor responses to therapy. The TP53 protein functions as a homo-tetrameric transcription factor, directly regulating the expression of similar to 500 target genes, some of them involved in cell death, cell cycling, cell senescence, DNA repair and metabolism. Originally, it was thought that the induction of apoptotic cell death was the principal mechanism by which TP53 prevents the development of tumours. However, gene targeted mice lacking the critical effectors of TP53-induced apoptosis (PUMA and NOXA) do not spontaneously develop tumours. Indeed, even mice lacking the critical mediators for TP53-induced apoptosis, G1/S cell cycle arrest and cell senescence, namely PUMA, NOXA and p21, do not spontaneously develop tumours. This suggests that TP53 must activate additional cellular responses to mediate tumour suppression. In this review, we will discuss the processes by which TP53 regulates cell death, cell cycling/cell senescence, DNA damage repair and metabolic adaptation, and place this in context of current understanding of TP53-mediated tumour suppression.

Automated summary

TP53 is a crucial tumor suppressor that regulates various cellular processes to prevent tumorigenesis, including cell death, cell cycle, cell senescence, DNA repair, and metabolism. Mutations in the TP53 gene are commonly found in human cancers and are associated with poor responses to therapy. However, the mechanism by which TP53 suppresses tumors involves more than just inducing apoptotic cell death, as mice lacking critical effectors of TP53-induced apoptosis or cell cycle arrest and senescence do not spontaneously develop tumors.