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Abstract：
RAS proteins are conserved guanosine triphosphate (GTP) hydrolases (GTPases) that act as molecular binary switches and play vital roles in numerous cellular processes. Upon GTP binding, RAS GTPases adopt an active conformation and interact with specific proteins termed RAS effectors that contain a conserved ubiquitin-like domain, thereby facilitating downstream signaling. Over 50 effector proteins have been identified in the human proteome, and many have been studied as potential mediators of RAS-dependent signaling pathways. Biochemical and structural analyses have provided mechanistic insights into these effectors, and studies using model organisms have complemented our understanding of their role in physiology and disease. Yet, many critical aspects regarding the dynamics and biological function of RAS-effector complexes remain to be elucidated. In this review, we discuss the mechanisms and functions of known RAS effector proteins, provide structural perspectives on RAS-effector interactions, evaluate their significance in RAS-mediated signaling, and explore their potential as therapeutic targets.
摘要：
RAS蛋白是保守的三磷酸鸟苷(GTP)水解酶(GTPases),其充当分子二元开关并在许多细胞过程中发挥重要作用。在GTP结合时，RASGTPases采用活性构象，并与包含保守的泛素样结构域的称为RAS效应子的特定蛋白质相互作用，从而促进下游信令。在人类蛋白质组中已经鉴定出超过50种效应蛋白,和许多已经被研究为RAS依赖性信号通路的潜在介质。生物化学和结构分析提供了对这些效应物的机械见解，使用模式生物的研究补充了我们对它们在生理和疾病中作用的理解。然而，关于RAS效应子复合物的动力学和生物学功能的许多关键方面仍有待阐明。在这次审查中,我们讨论了已知RAS效应蛋白的机制和功能，提供RAS-效应器相互作用的结构观点，评估它们在RAS介导的信号传导中的意义，并探索它们作为治疗靶点的潜力。
