Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Cell Adh Migr. 2010 Jan-Mar;4(1):10-8. doi: 10.4161/cam.4.1.9834. Epub 2010 Jan 18.
Recent studies have demonstrated that a number of E3 ubiquitin ligases, including Cbl, Smurf1, Smurf2, HDM2, BCA2, SCF(beta-TRCP) and XRNF185, play important roles in cell adhesion and migration. Cbl negatively regulates cell adhesion via alpha integrin and Rap1 and inhibits actin polymerization by ubiquitinating mDab1 and WAVE2. Smurf1 regulates cell migration through ubiquitination of RhoA, talin head domain and hPEM2, while Smurf2 ubiquitinates Smurf1, TGFbeta type I receptor and RaplB to modulate cell migration and adhesion. HDM2 negatively regulates cell migration by targeting NFAT (a transcription factor) for ubiquitination and degradation, while SCF(beta-TRCP) ubiquitinates Snail (a transcriptional repressor of E-cadherin) to inhibit cell migration. TRIM32 promotes cell migration through ubiquitination of Abl interactor 2 (Abi2), a tumor suppressor. RNF5 and XRNF185 modulate cell migration by ubiquitinating paxillin. Thus, these E3 ubiquitin ligases regulate cell adhesion and (or) migration through ubiquitination of their specific substrates.
最近的研究表明，包括 Cbl、Smurf1、Smurf2、HDM2、BCA2、SCF(beta-TRCP) 和 XRNF185 在内的许多 E3 泛素连接酶在细胞黏附和迁移中发挥重要作用。Cbl 通过 α 整合素和 Rap1 负调控细胞黏附，并通过泛素化 mDab1 和 WAVE2 抑制肌动蛋白聚合。Smurf1 通过泛素化 RhoA、talin 头部结构域和 hPEM2 来调节细胞迁移，而 Smurf2 则通过泛素化 Smurf1、TGFbeta 型 I 受体和 RaplB 来调节细胞迁移和黏附。HDM2 通过靶向 NFAT（一种转录因子）进行泛素化和降解来负调控细胞迁移，而 SCF(beta-TRCP) 则通过泛素化 Snail（E-钙黏蛋白的转录抑制因子）来抑制细胞迁移。TRIM32 通过泛素化 Abl 相互作用蛋白 2（Abi2），一种肿瘤抑制因子，促进细胞迁移。RNF5 和 XRNF185 通过泛素化粘着斑激酶（FAK）来调节细胞迁移。因此，这些 E3 泛素连接酶通过泛素化其特定底物来调节细胞黏附和（或）迁移。
