MDM2 and neoplasm: Furthermore, USP7 plays key roles in the p53 tumor suppressor pathway through stabilization of p53 via increasing MDM2, the E3 ligase largely responsible for the ubiquitination of p53 [6, 52]; while USP22 is reported to antagonize p53 transcriptional activation by deubiquitinating Sirt1 which deacytatates p53 and reduces its transcriptional activity [34].