[p53]

The gene coding p53 is commonly affected by deletions, rearrangements, or point mutations in a variety of human cancers. p53 is a nuclear phosphoprotein. Mutations are frequently found at highly conserved residues of the p53 protein. The mutant p53 proteins examined so far each have a much longer half-life than that of the wild-type p53 protein which is rapidly degraded under normal conditions. Alterations of p53 protein conformation result in the accumulation of such protein usually in transformed cells or cancer cells. The p53 protein is a sequence-specific DNA-binding protein that is active as a transcription factor. The genes coding p21, GADD45, mdm2, cyclin G etc. contain such a p53 responsive element. Upon exposure of cells to ionizing radiation, ultraviolet light, or DNA-damaging agents, high levels of p53 accumulate, resulting in subsequent stimulation of a series of p53-responsive genes and cell cycle arrest or apoptosis. The function of p53 is also linked to DNA synthesis via interaction with p21 and PCNA. The pathways involving p53 seem to be extremely complicated but may play an important role in the core function of cell growth.