p53
Reviewed by Maurice Lichtenberg
p53 is a tumour-suppressor protein encoded by the TP53 gene that acts as a central transcription factor in the cellular response to genotoxic stress, hypoxia, oncogene activation and nutrient deprivation. Upon activation, it induces transcriptional programmes that can drive cell-cycle arrest, DNA repair, apoptosis or senescence, with the outcome depending on stress intensity, cell type and co-regulatory context. Because p53-dependent senescence and apoptosis both limit the proliferation of damaged cells, p53 plays a dual role in ageing: it suppresses tumours yet, when chronically active, can deplete stem-cell pools and reinforce senescent-cell accumulation. Germline TP53 variants and somatic TP53 mutations are the most common alterations found in human cancers, and altered p53 activity is implicated in multiple age-related pathologies beyond malignancy.
