SCF FBXW17 E3 ubiquitin ligase regulates FBXL19 stability and cell migration,Journal of Cellular Biochemistry

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SCF FBXW17 E3 ubiquitin ligase regulates FBXL19 stability and cell migration
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2020-10-14 , DOI: 10.1002/jcb.29860
Su Dong ₁ , Jianxin Wei ₂ , Rachel K Bowser ₂ , Bill B Chen ₂ , Rama K Mallampalli ₃ , Jiaxing Miao ₁ , Qinmao Ye ₁ , Kevin C Tran ₁ , Yutong Zhao _{1,

3} , Jing Zhao _{1,

3}

Affiliation

The Skp1‐Cul1‐F‐box protein (SCF) E3 ligase complex is one of the largest ubiquitin E3 ligase families. FBXL19, a F‐box protein in SCF^FBXL19 E3 ligase complex, regulates a variety of cellular responses including cell migration. We have shown that FBXL19 is not stable and its degradation is mediated by the ubiquitin–proteasome system, while the ubiquitin E3 ligase for FBXL19 ubiquitination and degradation has not been identified. In the study, we discovered that a new ubiquitin E3 ligase, SCF^FBXW17, ubiquitinates and induces FBXL19 degradation. Exogenous FBXW17 targets FBXL19 for its ubiquitination and degradation. Lysine 114 in FBXL19 is a potential ubiquitin acceptor site. Acetylation of FBXL19 attenuated SCF^FBXW17‐mediated FBXL19 degradation. SCF^FBXL19 E3 ligase reduced Rac1 levels and cell migration, while the effects were attenuated by exogenous FBXW17. Downregulation of FBXW17 attenuated lysophosphatidic acid‐induced lamellipodia formation and Rac1 accumulation at migration leading edge. Taken together with our previous studies, FBXL19 is degraded by the ubiquitin–proteasome system and its site‐specific ubiquitination is mediated by SCF^FBXW17 E3 ligase, which promotes cell migration.

中文翻译：

SCF FBXW17 E3 泛素连接酶调节 FBXL19 稳定性和细胞迁移

Skp1-Cul1-F-box 蛋白 (SCF) E3 连接酶复合物是最大的泛素 E3 连接酶家族之一。^{FBXL19 是 SCF FBXL19} E3 连接酶复合物中的一种 F-box 蛋白，可调节多种细胞反应，包括细胞迁移。我们已经证明 FBXL19 不稳定，其降解由泛素-蛋白酶体系统介导，而用于 FBXL19 泛素化和降解的泛素 E3 连接酶尚未确定。在这项研究中，我们发现一种新的泛素 E3 连接酶 SCF ^FBXW17泛素化并诱导 FBXL19 降解。外源性 FBXW17 针对 FBXL19 进行泛素化和降解。FBXL19 中的赖氨酸 114 是一个潜在的泛素受体位点。FBXL19 的乙酰化减弱了 SCF ^FBXW17介导的 FBXL19 降解。供应链金融^FBXL19 E3 连接酶降低了 Rac1 水平和细胞迁移，而外源性 FBXW17 减弱了这种影响。FBXW17 的下调减弱了溶血磷脂酸诱导的片状伪足形成和迁移前缘的 Rac1 积累。结合我们之前的研究，FBXL19 被泛素-蛋白酶体系统降解，其位点特异性泛素化由促进细胞迁移的 SCF ^{FBXW17 E3 连接酶介导。}

更新日期：2020-10-14

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