Up-regulated oxidized USP2a can increase Mdm2-p60-p53 to promote cell apoptosis
Up-regulated oxidized USP2a can increase Mdm2-p60-p53 to promote cell apoptosis
复制标题
DOI：
10.1016/j.yexcr.2023.113597
复制
发表时间：
2023-04-14
影响因子：
3.7
通讯作者：
Gao，Fenghou
中科院分区：
文献类型：
--
作者：
Zhu，Hanqing;Zhang，Hongliang;Gao，Fenghou
Mdm2促进p53泛素化和降解，而Mdm2-p60可以与p53结合，减少Mdm2诱导的p53泛素化，提高其稳定性。 USP2a可以去泛素化并稳定Mdm2，USP2a是否可以调节Mdm2-p60需要进一步证实和阐明。我们发现氧化应激可以在转录后水平上调USP2a，并通过形成亚基间二硫键诱导USP2a被氧化。氧化的USP2a与细胞凋亡密切相关。在凋亡细胞中，氧化的USP2a增强了蛋白质稳定性，并通过去泛素化进一步稳定Mdm2-p60，USP2a-Mdm2-p60-p53轴在细胞凋亡中发挥作用。总之，USP2a对氧敏感，氧化后的USP2a通过Mdm2-p60-p53轴发挥凋亡作用，这为靶向USP2a调控p53凋亡信号提供了实验基础。
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.