Posttranslational phosphorylation of mutant p53 protein in tumor development

p53 has been called the “cellular gatekeeper” and the “genome guard,” because in response to exposure to DNA-damaging agents, it induces cell-cycle arrest in G1 or apoptosis and also directly affects DNA replication. Multiple mechanisms regulate p53 activity and posttranslational modification, including multisite phosphorylation of wild-type p53, in particular. Normal functions of wild-type p53 are abrogated by mutation of this gene, and oncogenic studies have revealed that p53 mutation is among the most common genetic alteration in human cancers. It is generally accepted that mutant p53 protein may not only lose the tumor suppressor functions of wild-type p53 but also acquire additional tumorigenetic roles, including dominant-negative effects and gain of function. Although many studies have revealed such aberrant functions of mutant p53, less is known about the posttranslational phosphorylation status of mutant p53 and novel biological functions of phosphorylation in carcinogenesis.