The role of ubiquitylation and degradation in RhoGTPase signalling
The role of ubiquitylation and degradation in RhoGTPase signalling
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DOI：
10.1242/jcs.078360
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发表时间：
2010-12-01
影响因子：
4
通讯作者：
Hordijk, Peter L.
中科院分区：
文献类型：
--
作者：
Nethe, Micha;Hordijk, Peter L.
Rho样鸟苷三磷酸酶(RhoGTPase)通过对肌动蛋白细胞骨架和基因转录的影响，控制着细胞生理的许多方面。RhoGTP酶的信号传递是紧密协调的，需要一系列调节蛋白，包括鸟嘌呤核苷酸交换因子(GEF)、GTP酶激活蛋白(GAP)和鸟嘌呤核苷酸解离抑制物(GDIs)。GEFS和GAP调节GTP酶在激活状态(GTP结合)和非激活状态(GDP结合)之间的循环，而GDI是一个胞质伴侣，它结合不活跃的RhoGTP酶。像许多其他蛋白质一样，RhoGTP酶在泛素共价连接后容易降解。越来越多的迹象表明，小GTP酶的泛素化是以一种受调控的方式发生的，主要是在激活时发生的，是控制信号输出的重要手段。最近的工作已经确定了控制RasGTP酶和RhoGTP酶泛素化和降解的细胞蛋白质，使我们能够修正GTP酶(IN)激活的规范模型。此外，越来越多的证据表明，通过GTP酶调节因子的泛素化间接调节GTP酶的功能，使这种翻译后修饰成为GTP酶依赖的信号通路的关键特征。在这里，我们将讨论这些关于RhoGTP酶泛素化调控的最新见解及其与细胞信号的相关性。
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.