Post-translational modifications of RGS protein family: Pivotal switches in cellular signaling transduction and diseases.

Regulator of G protein signaling (RGS) proteins are critical modulators of G protein-coupled receptor (GPCR) signaling through their GTPase-activating protein (GAP) activity. RGS proteins are regulated at multiple levels, including the pre-transcription, transcription, and post-translation levels. Among the regulation patterns, post-translational modification (PTMs) can directly affect the regulation of G protein signaling by modulating the GAP activity of RGS proteins or indirectly regulate their function by affecting their subcellular localization and stability. The corresponding PTM behavior of a certain RGS protein is regulated by complex upstream factors and is closely related to multiple downstream signal transduction associated with G proteins. This complex regulatory relationship forms a dynamic and fine-tuned regulatory network within the cell. In this review, we methodically summarize the impact of diverse PTMs on RGS proteins and provide a comprehensive overview of their associated upstream regulatory factors and downstream signal pathway alterations. Furthermore, we explore the physiological and pathological states associated with PTM dysregulation. Additionally, we discuss the potential clinical application value of PTMs targeting RGS.