Up-regulated oxidized USP2a can increase Mdm2-p60-p53 to promote cell apoptosis

Mdm2 promotes the ubiquitination and degradation of p53, while Mdm2-p60 can bind to p53 and reduce the Mdm2-induced p53 ubiquitination to improve its stability. USP2a can deubiquitinate and stabilize Mdm2, whether USP2a can regulate Mdm2-p60 needs to be further confirmed and elucidated. We found that oxidative stress can up-regulate USP2a at the post-transcriptional level and induce USP2a to be oxidized by forming inter-subunit disulfide bonds. The oxidized USP2a is closely related with cell apoptosis. In apoptotic cells, oxidized USP2a has enhanced protein stability and further stabilizes Mdm2-p60 through deubiquitination, and the USP2a-Mdm2-p60-p53 axis plays a role in cell apoptosis. Altogether USP2a is oxygen sensitive, oxidized USP2a exerts apoptotic effects through the Mdm2-p60-p53 axis, which provides an experimental basis for regulating p53 apoptotic signaling by targeting USP2a.

Automated summary

Mdm2 promotes the degradation of p53, while Mdm2-p60 can bind to p53 and stabilize it. USP2a stabilizes Mdm2, and its role in regulating Mdm2-p60 needs further investigation. We found that oxidative stress up-regulates USP2a and induces its oxidation, which is closely related to cell apoptosis. In apoptotic cells, oxidized USP2a stabilizes Mdm2-p60 and plays a role in cell apoptosis. This provides an experimental basis for targeting USP2a to regulate p53 apoptotic signaling.