USP37 is a SNAI1 deubiquitinase.
USP37 is a SNAI1 deubiquitinase.
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发表时间：
2019-12
影响因子：
5.3
通讯作者：
Zhenna Xiao;Liang Chang;Jongchan Kim;Peijing Zhang;Qinglei Hang;Shannon Yap;Youming Guo;Zhicheng Zhou;Liyong Zeng;Xiaoyu Hu;Ashley N. Siverly;Yutong Sun;Li Ma
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文献类型：
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作者：
Zhenna Xiao;Liang Chang;Jongchan Kim;Peijing Zhang;Qinglei Hang;Shannon Yap;Youming Guo;Zhicheng Zhou;Liyong Zeng;Xiaoyu Hu;Ashley N. Siverly;Yutong Sun;Li Ma
SNAI 1是一种上皮-间质转化（EMT）诱导转录因子，可促进肿瘤转移和对凋亡和化疗的抵抗。SNAI 1蛋白水平受到蛋白水解泛素化的严格调控。在这里，我们确定USP 37作为SNAI 1去泛素化酶，从SNAI 1去除多聚泛素化链，并防止其蛋白酶体降解。USP 37直接结合、去泛素化和稳定SNAI 1。野生型USP 37的过表达，而不是其催化失活突变体C350 S，促进癌细胞迁移。重要的是，USP 37的缺失下调内源性SNAI 1蛋白并抑制细胞迁移，这可以通过SNAI 1的重新表达来逆转。综上所述，我们的研究结果表明USP 37是SNAI 1去泛素化酶，是抑制肿瘤转移的潜在治疗靶点。
SNAI1, an epithelial-mesenchymal transition (EMT)-inducing transcription factor, promotes tumor metastasis and resistance to apoptosis and chemotherapy. SNAI1 protein levels are tightly regulated by proteolytic ubiquitination. Here, we identified USP37 as a SNAI1 deubiquitinase that removes the polyubiquitination chain from SNAI1 and prevents its proteasomal degradation. USP37 directly binds, deubiquitinates, and stabilizes SNAI1. Overexpression of wild-type USP37, but not its catalytically inactive mutant C350S, promotes cancer cell migration. Importantly, depletion of USP37 downregulates endogenous SNAI1 protein and suppresses cell migration, which can be reversed by re-expression of SNAI1. Taken together, our findings suggest that USP37 is a SNAI1 deubiquitinase and a potential therapeutic target to inhibit tumor metastasis.