FUNCTIONAL DISSECTION OF P53 TUMOR SUPPRESSOR PROTEIN

Publisher Summary This chapter discusses the functional dissection of p53 tumor suppressor protein. The p53 tumor suppressor protein plays a pivotal role in tumor suppression and is mutated very frequently in many forms of human cancer. Stress signals such as DNA damage and hypoxia cause the induction and activation of p53 in normal cells with the ensuing response of repression of cell growth and division. There are two modes by which p53 restrain cells after genotoxic stress: cell cycle arrest and cell death. The importance of DNA binding to p53 function is underscored by the facts that the majority of tumor-derived mutant forms of p53 are defective in DNA binding, and their mutations are located within the sequence-specific DNA binding domain that is within the central region of p53. Although a number of reports have identified a transcription-independent function of p53 in inducing apoptosis, the data suggest that p53 DNA binding is likely to be involved in this function as well.