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Updated: Aug 3, 2025

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
Up-regulated oxidized USP2a can increase Mdm2-p60-p53 to promote cell apoptosis
Hanqing Zhu1, Hongliang Zhang2, Jiahui Guo3
1Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
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.
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