Post-Translational Modifications (PTMs) of mutp53 and Epigenetic Changes Induced by mutp53

Post-translational modifications (PTMs) strongly influence the stability and function of proteins. These modifications have been reported to affect wild-type (wt) p53 as well as the mutant forms of this protein (mutp53), often detected in cancer cells. Thus, PTMs may be key regulators of the oncosuppressor activity of wtp53 and of the pro-oncogenic functions that some mutant forms of p53 may acquire, in terms of tumor survival, progression and resistance to anti-cancer therapies. As treatments that specifically target mutp53 do not exist, manipulating PTMs may represent a promising approach to achieve this goal and even to reactivate the wt functions of mutant proteins, in some cases, as reported in this review.Abstract Wild-type (wt) p53 and mutant forms (mutp53) play a key but opposite role in carcinogenesis. wtP53 acts as an oncosuppressor, preventing oncogenic transformation, while mutp53, which loses this property, may instead favor this process. This suggests that a better understanding of the mechanisms activating wtp53 while inhibiting mutp53 may help to design more effective anti-cancer treatments. In this review, we examine possible PTMs with which both wt- and mutp53 can be decorated and discuss how their manipulation could represent a possible strategy to control the stability and function of these proteins, focusing in particular on mutp53. The impact of ubiquitination, phosphorylation, acetylation, and methylation of p53, in the context of several solid and hematologic cancers, will be discussed. Finally, we will describe some of the recent studies reporting that wt- and mutp53 may influence the expression and activity of enzymes responsible for epigenetic changes such as acetylation, methylation, and microRNA regulation and the possible consequences of such changes.