Lin Yuan, Zheng Yi
Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; University of Cincinnati College of Medicine, Cincinnati, OH, USA.
J Mol Biol. 2025 Feb 1;437(3):168919. doi: 10.1016/j.jmb.2024.168919. Epub 2024 Dec 19.
Rho family GTPases are a part of the Ras superfamily and are signaling hubs for many cellular processes. While the detailed understanding of Ras structure and function has led to tremendous progress in oncogenic Ras-targeted drug discovery, studies of the related Rho GTPases are still catching up as the recurrent cancer-related Rho GTPase mutations have only been discovered in the last decade. Like that of Ras, an in-depth understanding of the structural basis of how Rho GTPases and their mutants behave as key oncogenic drivers benefits the development of clinically effective therapies. Recent studies of structure dynamics in Rho GTPase structure-function relationship have added new twists to the conventional wisdom of Rho GTPase signaling mechanism.
Rho家族GTP酶是Ras超家族的一部分,是许多细胞过程的信号枢纽。虽然对Ras结构和功能的详细了解在靶向致癌Ras的药物发现方面取得了巨大进展,但相关Rho GTP酶的研究仍在追赶,因为与癌症复发相关的Rho GTP酶突变直到最近十年才被发现。与Ras一样,深入了解Rho GTP酶及其突变体作为关键致癌驱动因子的结构基础,有利于临床有效疗法的开发。最近关于Rho GTP酶结构-功能关系中结构动力学的研究,给Rho GTP酶信号传导机制的传统认知带来了新变化。