Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich Heine University, Universitätsstrasse 1, Building 22.03.05, 40225 Düsseldorf, Germany.
Cells. 2021 Jul 20;10(7):1831. doi: 10.3390/cells10071831.
Much progress has been made toward deciphering RHO GTPase functions, and many studies have convincingly demonstrated that altered signal transduction through RHO GTPases is a recurring theme in the progression of human malignancies. It seems that 20 canonical RHO GTPases are likely regulated by three GDIs, 85 GEFs, and 66 GAPs, and eventually interact with >70 downstream effectors. A recurring theme is the challenge in understanding the molecular determinants of the specificity of these four classes of interacting proteins that, irrespective of their functions, bind to common sites on the surface of RHO GTPases. Identified and structurally verified hotspots as functional determinants specific to RHO GTPase regulation by GDIs, GEFs, and GAPs as well as signaling through effectors are presented, and challenges and future perspectives are discussed.
在破译 RHO GTPase 功能方面已经取得了很大进展，许多研究令人信服地表明，通过 RHO GTPase 的信号转导改变是人类恶性肿瘤进展中的一个反复出现的主题。似乎 20 个典型的 RHO GTPase 可能受到三种 GDIs、85 种 GEF 和 66 种 GAP 的调节，最终与 >70 种下游效应物相互作用。一个反复出现的主题是理解这四类相互作用蛋白的特异性的分子决定因素的挑战，这些蛋白无论其功能如何，都结合到 RHO GTPase 表面的共同部位。本文介绍了作为功能决定因素的已鉴定和结构验证的热点，这些热点是特定于 GDI、GEF 和 GAP 对 RHO GTPase 的调节以及通过效应物进行信号转导的，同时讨论了挑战和未来展望。
