miRNAs 和共价修饰对 Rho GTPase 的调节。
Rho GTPase regulation by miRNAs and covalent modifications.
机构信息
Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, OH 45229, USA.
出版信息
Trends Cell Biol. 2012 Jul;22(7):365-73. doi: 10.1016/j.tcb.2012.04.004. Epub 2012 May 7.
To date, most studies of Rho GTPase regulation have focused on the classic GTPase cycle - GTP binding and hydrolysis - controlled by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and GDP-dissociation inhibitors (GDIs). Recent investigations have unveiled important additional regulatory mechanisms: microRNA (miRNA) regulating post-transcriptional processing of Rho GTPase-encoding mRNAs; palmitoylation and nuclear targeting affecting intracellular distribution; post-translational phosphorylation, transglutamination and AMPylation impacting Rho GTPase signaling; and ubiquitination controlling Rho GTPase protein stability and turnover. These modes of regulation add to the complexity of the Rho GTPase signaling network and allow precise spatiotemporal control of individual Rho GTPases. This review discusses these 'unconventional' modes of regulation and their contribution to cellular function, focusing on post-transcriptional and post-translational events beyond the classic GTPase cycle regulatory model.
迄今为止，大多数关于 Rho GTPase 调控的研究都集中在经典的 GTPase 循环上——由鸟嘌呤核苷酸交换因子（GEFs）、GTPase 激活蛋白（GAPs）和 GDP 解离抑制剂（GDIs）控制的 GTP 结合和水解。最近的研究揭示了重要的额外调控机制：微小 RNA（miRNA）调控 Rho GTPase 编码 mRNA 的转录后加工；棕榈酰化和核靶向影响细胞内分布；翻译后磷酸化、转谷氨酰胺和 AMP 化影响 Rho GTPase 信号转导；泛素化控制 Rho GTPase 蛋白稳定性和周转。这些调控模式增加了 Rho GTPase 信号网络的复杂性，并允许对单个 Rho GTPase 进行精确的时空控制。本文讨论了这些“非常规”调控模式及其对细胞功能的贡献，重点关注经典 GTPase 循环调控模型之外的转录后和翻译后事件。
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