The p53 network: cellular and systemic DNA damage responses in cancer and aging

The tumor protein TP53 gene, encoding the cellular tumor antigen p53, is the single most frequently mutated gene in human cancers. p53 plays a central role in responding to DNA damage and determines the outcome of the DNA damage checkpoint response by regulating cell cycle arrest and apoptosis. As a consequence of this function, dysfunctional p53 results in cells that, despite a damaged genome, continue to proliferate thus fueling malignant transformation. New insights have recently been gained into the complexity of the p53 regulation of the DNA damage response (DDR) and how it impacts a wide variety of cellular processes. In addition to cell-autonomous signaling mechanisms, non-cell-autonomous regulatory inputs influence p53 activity, which in turn can have systemic consequences on the organism. New inroads have also been made toward therapeutic targeting of p53 that for a long time has been anticipated.

Automated summary

The TP53 gene is the most frequently mutated gene in human cancers, and p53 plays a crucial role in responding to DNA damage. Dysfunctional p53 leads to continued proliferation of cells with damaged genome, promoting malignant transformation. Recent research has shed light on the complexity of p53 regulation in the DNA damage response, as well as its systemic effects influenced by non-cell-autonomous signaling mechanisms. There have also been advancements in therapeutic targeting of p53.