PDF(Pubmed)
Abstract：
Despite the critical role of Rab GTPases for intracellular transport, the vast majority of proteins within this family remain poorly characterized, including the Rab40 subfamily. Often recognized as atypical Rabs, the Rab40 family of proteins are unlike any other small GTPase because they contain a C-terminal suppressor of cytokine signaling (SOCS) box. It is well established that this SOCS domain in other proteins mediates an interaction with the scaffold protein Cullin5 in order to form a E3 ubiquitin ligase complex critical for protein ubiquitylation and turnover. Although the function of SOCS/Cullin5 complexes has been well defined in several of these other proteins, this is not yet the case for the Rab40 family of proteins. We have previously shown that the Rab40b family member plays an important role during three-dimensional (3D) breast cancer cell migration. To further this knowledge, we began to investigate the SOCS-dependent role of Rab40b during cell migration. Here, we describe an unbiased approach to identify potential Rab40b/Cullin5 substrates. We anticipate that this method will be useful for studying the function of other Rab40 family members as well as other SOCS box containing proteins.
摘要：
尽管RabGTP酶在细胞内转运中的关键作用，这个家族中的绝大多数蛋白质特征仍然很差，包括Rab40家族.通常被认为是非典型的兔子，Rab40蛋白家族不同于任何其他小的GTP酶,因为它们含有细胞因子信号传导(SOCS)盒的C末端抑制剂。已经确定，其他蛋白质中的此SOCS结构域介导与支架蛋白Cullin5的相互作用，以形成对蛋白质泛素化和周转至关重要的E3泛素连接酶复合物。尽管SOCS/Cullin5复合物的功能已经在其他几种蛋白质中得到了很好的定义，Rab40蛋白家族还没有出现这种情况。我们先前已经表明，Rab40b家族成员在三维（3D）乳腺癌细胞迁移中起着重要作用。为了进一步了解这些知识，我们开始研究Rab40b在细胞迁移过程中的SOCS依赖性作用。这里,我们描述了一种无偏见的方法来识别潜在的Rab40b/Cullin5底物。我们预计该方法将用于研究其他Rab40家族成员以及其他含有SOCS盒的蛋白质的功能。
