P53 mutations in human cancer.

A 53,000 dalton protein called p53, was noted to be mutated in human cancer in 1987. Further studies have shown that p53 is a tumor suppressor gene which may be one of the most frequently altered genes in cancer of all types. These alterations include interactions with viral antigens, coding mutations and inactivating rearrangements. Accumulating evidence suggests that p53 acts by binding DNA and activating transcription. Expression of p53 after transfection with a constitutive promotor, blocks cellular proliferation and leads to an apoptotic cell death. In normal cells, p53 expression is induced by irradiation; this has led to the hypothesis that p53 acts to inhibit replication during genetic repair. Cells which lack p53 are more prone to develop amplification. Mice lacking p53 are born normal but develop cancer after a lag of months, this suggests that p53 is not an initiating mutation in cancer, but probably a late event.