Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
J Cell Sci. 2010 Dec 1;123(Pt 23):4011-8. doi: 10.1242/jcs.078360.
Rho-like guanosine triphosphatases (RhoGTPases) control many aspects of cellular physiology through their effects on the actin cytoskeleton and on gene transcription. Signalling by RhoGTPases is tightly coordinated and requires a series of regulatory proteins, including guanine-nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and guanine-nucleotide dissociation inhibitors (GDIs). GEFs and GAPs regulate GTPase cycling between the active (GTP-bound) and inactive (GDP-bound) states, whereas GDI is a cytosolic chaperone that binds inactive RhoGTPases. Like many other proteins, RhoGTPases are subject to degradation following the covalent conjugation of ubiquitin. There have been increasing indications that ubiquitylation of small GTPases occurs in a regulated fashion, primarily upon activation, and is an important means to control signalling output. Recent work has identified cellular proteins that control RasGTPase and RhoGTPase ubiquitylation and degradation, allowing us to amend the canonical model for GTPase (in)activation. Moreover, accumulating evidence for indirect regulation of GTPase function through the ubiquitylation of GTPase regulators makes this post-translational modification a key feature of GTPase-dependent signalling pathways. Here, we will discuss these recent insights into the regulation of RhoGTPase ubiquitylation and their relevance for cell signalling.
Rho 样鸟苷三磷酸酶（RhoGTPases）通过对肌动蛋白细胞骨架和基因转录的影响来控制细胞生理的许多方面。RhoGTPases 的信号传递受到严格协调，需要一系列调节蛋白，包括鸟嘌呤核苷酸交换因子（GEFs）、GTPase 激活蛋白（GAPs）和鸟嘌呤核苷酸解离抑制剂（GDIs）。GEFs 和 GAPs 调节 GTPase 在活性（GTP 结合）和非活性（GDP 结合）状态之间的循环，而 GDI 是一种胞质伴侣，可结合非活性的 RhoGTPases。像许多其他蛋白质一样，RhoGTPases 在共价结合泛素后会发生降解。越来越多的迹象表明，小 GTPases 的泛素化是一种受调控的方式，主要在激活时发生，是控制信号输出的重要手段。最近的工作已经确定了控制 RasGTPase 和 RhoGTPase 泛素化和降解的细胞蛋白，使我们能够修正 GTPase（失活）的经典模型。此外，通过 GTPase 调节因子的泛素化间接调节 GTPase 功能的累积证据表明，这种翻译后修饰是 GTPase 依赖性信号通路的关键特征。在这里，我们将讨论这些关于 RhoGTPase 泛素化调节的最新见解及其与细胞信号转导的相关性。
