p 53 : Structure , Function and Therapeutic Applications

Since the p53 tumor suppressor gene has been found to be mutated in more than 50% of human cancers, it has attracted the interest of numerous researchers. The capacity of p53 for multiple biological functions can be attributed to its ability to act as a sequence-specific transcription factor to regulate expression of over one hundred different targets, and thus to modulate various cellular processes including apoptosis, cell cycle arrest and DNA repair. The p53 protein with its unique Cand N-terminal structures is rigidly modulated by several important biological processes such as phosphorylation, acetylation and ubiquitination, through which it effectively regulates cell growth and cell death. p53 mutations can lead either to loss or change of p53 binding activity to its downstream targets and may thus induce aberrant cell proliferation, with consequent malignant cellular transformation. Based on p53’s critical role in carcinogenesis, scientists have developed multiple effective strategies for treating cancer by enhancing function of wild-type p53 or increasing p53 stability. This review will focus on (i) discussing of the relationship between p53 structure and function, (ii) p53 mutations, and (iii) recent strategies for improving the efficacy of cancer treatment by therapeutic manipulation of p53.