{Reference Type}: Journal Article
{Title}: Up-regulated oxidized USP2a can increase Mdm2-p60-p53 to promote cell apoptosis.
{Author}: Zhu H;Zhang H;Guo J;Zhang C;Zhang Q;Gao F;
{Journal}: Exp Cell Res
{Volume}: 427
{Issue}: 1
{Year}: 06 2023 1
{Factor}: 4.145
{DOI}: 10.1016/j.yexcr.2023.113597
{Abstract}: 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.