The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression

Abstract

P53 is a transcription factor highly inducible by many stress signals such as DNA damage, oncogene activation, and nutrient deprivation. Cell-cycle arrest and apoptosis are the most prominent outcomes of p53 activation. Many studies showed that p53 cell-cycle and apoptosis functions are important for preventing tumor development. p53 also regulates many cellular processes including metabolism, antioxidant response, and DNA repair. Emerging evidence suggests that these noncanonical p53 activities may also have potent antitumor effects within certain context. This review focuses on the cell-cycle arrest and apoptosis functions of p53, their roles in tumor suppression, and the regulation of cell fate decision after p53 activation.

Figure 1.

p53 induces different target genes to block different stages of tumor development. Metabolic/antioxidant/DNA repair genes reduce the chance of spontaneous tumor initiation by maintaining homeostasis, reducing mutation rates, blocking epigenetic changes, and promoting DNA damage repair. When tumors pass the initiation step, tumor progression is blocked by apoptosis/cell-cycle arrest/senescence activities.