The first 30 years of p53: growing ever more complex

When p53 was first discovered, it received relatively little attention from cancer researchers. The road leading to p53's rise to fame, and the recognition of TP53 as the most frequently altered gene in human cancer, has been long and winding. This Timeline examines the rich history of this pivotal tumour suppressor. Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus. The first decade of p53 research saw the cloning of p53 DNA and the realization that p53 is not an oncogene but a tumour suppressor that is very frequently mutated in human cancer. In the second decade of research, the function of p53 was uncovered: it is a transcription factor induced by stress, which can promote cell cycle arrest, apoptosis and senescence. In the third decade after its discovery new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation. The fourth decade of research may see new p53-based drugs to treat cancer. What is next is anybody's guess.