文章：

ERK3通过抑制FBXO11介导的Snail泛素化增强Snail蛋白稳定性

ERK3 Increases Snail Protein Stability by Inhibiting FBXO11-Mediated Snail Ubiquitination

原文发布日期：24 December 2023

DOI: 10.3390/cancers16010105

类型: Article

开放获取: 是

英文摘要：

Snail is a key regulator of the epithelial-mesenchymal transition (EMT), the key step in the tumorigenesis and metastasis of tumors. Although induction of Snail transcription precedes the induction of EMT, the post-translational regulation of Snail is also important in determining Snail protein levels, stability, and its ability to induce EMT. Several kinases are known to enhance the stability of the Snail protein by preventing its ubiquitination; however, the precise molecular mechanisms by which these kinases prevent Snail ubiquitination remain unclear. Here, we identified ERK3 as a novel kinase that interacts with Snail and enhances its protein stability. Although ERK3 could not directly phosphorylate Snail, Erk3 increased Snail protein stability by inhibiting the binding of FBXO11, an E3 ubiquitin ligase that can induce Snail ubiquitination and degradation, to Snail. Importantly, functional studies and analysis of clinical samples indicated the crucial role of ERK3 in the regulation of Snail protein stability in pancreatic cancer. Therefore, we conclude that ERK3 is a key regulator for enhancing Snail protein stability in pancreatic cancer cells by inhibiting the interaction between Snail and FBXO11.

摘要翻译： 

Snail是上皮-间质转化（EMT）的关键调控因子，而EMT是肿瘤发生与转移的核心环节。尽管Snail的转录诱导先于EMT的启动，但其翻译后修饰对Snail蛋白水平、稳定性及其诱导EMT能力的调控同样至关重要。已知多种激酶可通过阻止Snail泛素化来增强其稳定性，然而这些激酶抑制Snail泛素化的具体分子机制尚不明确。本研究发现，ERK3作为一种新型激酶可与Snail相互作用并增强其蛋白稳定性。虽然ERK3不能直接磷酸化Snail，但可通过抑制E3泛素连接酶FBXO11与Snail的结合来提升Snail蛋白稳定性，而FBXO11正是介导Snail泛素化降解的关键因子。重要的是，功能研究及临床样本分析均证实ERK3在胰腺癌Snail蛋白稳定性调控中发挥关键作用。因此我们得出结论：ERK3通过抑制Snail与FBXO11的相互作用，成为增强胰腺癌细胞中Snail蛋白稳定性的关键调控因子。

原文链接：

ERK3 Increases Snail Protein Stability by Inhibiting FBXO11-Mediated Snail Ubiquitination