Abstract
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.
Highlights
Snail is a member of SNAG domain-containing zinc finger transcription factors and a major regulator of epithelial–mesenchymal transition (EMT) and metastasis in various tumor types (Wang et al, 2013; Diaz et al, 2014)
We discover that USP37 directly binds Snail and markedly improves Snail protein stability through its deubiquitinase activity
Our studies showed that ectopically expressed Flag-USP37 was able to immunoprecipitate endogenous Snail protein in lung cancer H1299 cells (Figure 1C)
Summary
Snail is a member of SNAG domain-containing zinc finger transcription factors and a major regulator of epithelial–mesenchymal transition (EMT) and metastasis in various tumor types (Wang et al, 2013; Diaz et al, 2014). In accordance with its profound role in development and diseases, the level of Snail protein is tightly regulated through various extracellular signaling including transcription or protein degradation (Park et al, 2010; Suresh et al, 2016; Gudey et al, 2017). Several studies demonstrated that Snail can be quickly degraded via ubiquitinationmediated protein hydrolysis pathway (Suresh et al, 2016; Gudey et al, 2017). Several ring domain-containing E3 ligases, such as Fbxl (Wu et al, 2015), Fbxl
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