DUBs are demonstrated as a main regulator of apoptosis.[134] USP7 can remove Ub‐chain on Mdm2 conjugated by self‐ubiquitination, thus supporting Mdm2‐dependent p53 degradation.[135, 136] USP7 depletion stimulates MDM2 proteasomal degradation and promotes p53‐mediated apoptosis in tumor cells through stabilizing p53.[137, 138] In addition, p53 and MDM2 are also regulated by OTUB1, which controls p53 stabilization and activation by disrupting the interaction between p53 and MDM2.[139] Moreover, OTUB1 can stabilize murine double minute 4 (MDM4) by curbing MDM4 ubiquitination mediated by MDM2. This evidence concerns the gene MDM4 and neoplasm.