脱氮酶
泛素
基因敲除
化学
蛋白酶
癌症研究
细胞生物学
生物
计算生物学
生物化学
基因
酶
作者
Jianyuan Chen,Zishan Jiao,Yajing Liu,Meng Zhang,Donglai Wang
标识
DOI:10.1016/j.bbrc.2024.149818
摘要
Oncoprotein SE translocation (SET) is frequently overexpressed in different types of tumors and correlated with poor prognosis of cancer patients. Targeting SET has been considered a promising strategy for cancer intervention. However, the mechanisms by which SET is regulated under cellular conditions are largely unknown. Here, by performing a tandem affinity purification-mass spectrometry (TAP-MS), we identify ubiquitin-specific protease 7 (USP7) forms a stable protein complex with SET in cancer cells. Further analyses reveal that the acidic domain of SET directly binds USP7 while both catalytic domain and ubiquitin-like (UBL) domains of USP7 are required for SET binding. Knockdown of USP7 had no effect on the mRNA level of SET. However, we surprisingly find that USP7 depletion leads to a dramatic elevation of SET protein levels, suggesting that USP7 plays a key role in destabilizing oncoprotein SET, possibly through an indirect mechanism. To our knowledge, our data report the first deubiquitinase (DUB) that physically associates with oncoprotein SET and imply an unexpected regulatory effect of USP7 on SET stability.
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