Chiba Medical Society Young Investigator Award MinireviewApoptosis-inducing function of p53 and its mutations leading to cancer progression

ABSTRACTp53 plays an important role as one of the most well-known tumor suppressors. Under various stresses, p53 is stabilized and activated, and exerts functions involved in tumor suppression, including the induction of cell cycle arrest, apoptosis, and senescence. Among these, the induction of apoptosis is very important for preventing tumorigenesis. Stabilization of p53 is regulated by the ubiquitin ligase MDM2 or other proteins such as pARF14. In various cancer cells, TP53 gene mutations are found, and the loss of tumor-suppressive functions and gain of oncogenic functions in mutant p53 have been reported to lead to genomic instability and cancer progression. Herein, we summarize the mechanisms of apoptosis induction and the roles of p53 in this process, in which p53 has transactivation-dependent or transactivationindependent functions. In addition, we summarize the regulators of p53 and the mechanisms of p53 stabilization and activation, cancer-associated TP53 mutations, and functions of mutant p53. This review contributes to the understanding of the tumor-suppressive function of p53 and the significance of disrupted functions of mutant p53 as a target for therapeutic strategies.