USP37通过稳定蜗牛蛋白去泛素化促进肺癌细胞迁移。

Cai Jiali, Li Mengying, Wang Xiang, Li Lei, Li Qi, Hou Zhaoyuan, Jia Hao, Liu Shiyuan

Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Front Genet. 2020 Jan 10;10:1324. doi: 10.3389/fgene.2019.01324. eCollection 2019.

Snail is a prominent epithelial-mesenchymal transition (EMT) transcription factor and promotes metastasis. However, Snail protein is unstable and is quickly degraded through ubiquitination-mediated proteasome pathway. Deubiquitinases prevent Snail degradation by regulating the ubiquitination-mediated hydrolysis process. Our studies demonstrate that a deubiquitinating enzyme (DUB) family member, USP37, can deubiquitinate Snail and prevent degradation of Snail. USP37 is co-localized with Snail in the nucleus. Biologically, upregulated expression of USP37 promotes lung cancer cell migration, while depletion of Snail abolishes the effect of USP37. These data demonstrate that USP37 is a Snail-specific deubiquitinase and also indicate a potential therapeutic target for metastasis.

蜗牛蛋白是一种重要的上皮-间质转化（EMT）转录因子，可促进肿瘤转移。然而，蜗牛蛋白不稳定，会通过泛素化介导的蛋白酶体途径迅速降解。去泛素化酶通过调节泛素化介导的水解过程来阻止蜗牛蛋白的降解。我们的研究表明，去泛素化酶（DUB）家族成员USP37可以使蜗牛蛋白去泛素化并阻止其降解。USP37与蜗牛蛋白在细胞核中共定位。在生物学功能上，USP37表达上调促进肺癌细胞迁移，而敲低蜗牛蛋白则消除了USP37的作用。这些数据表明USP37是一种蜗牛蛋白特异性去泛素化酶，也提示了其作为转移治疗潜在靶点的可能性。