Tumor suppressor P53: Regulation and function

The p53 protein is a transcription factor involved in maintaining genomic i ntegrity by controlling cell cycle progression and cell survival. Mutations in p53 are the most frequently seen genetic alterations in human cancer. T he function of p53 is critical to the way many cancer treatments kill cells because radiotherapy and chemotherapy act in part by triggering programmed cell death in response to DNA damage. Consequently, tumors which bear p53 mutations, are often difficult to treat and their prognosis is poor. Since the underlying feature of tumors with p53 mutations is the absence of funct ional p53, gene replacement therapy with wild-type p53 gene is being consid ered as an approach for treating a variety of cancers. In recent years, mor e information has been obtained regarding various pathways leading to the a ctivation of p53, particularly those involving post-translational modificat ions of p53. Several new target genes of p53 have been identified. This rev iew will summarize current knowledge on the structure, mechanism of activat ion and effectors of p53 function.