RGS proteins and their roles in cancer: friend or foe?

As negative modulators of G-protein-coupled receptors (GPCRs) signaling, regulators of G protein signaling (RGS) proteins facilitate various downstream cellular signalings through regulating kinds of heterotrimeric G proteins by stimulating the guanosine triphosphatase (GTPase) activity of G-protein α (Gα) subunits. The expression of RGS proteins is dynamically and precisely mediated by several different mechanisms including epigenetic regulation, transcriptional regulation -and post-translational regulation. Emerging evidence has shown that RGS proteins act as important mediators in controlling essential cellular processes including cell proliferation, survival -and death via regulating downstream cellular signaling activities, indicating that RGS proteins are fundamentally involved in sustaining normal physiological functions and dysregulation of RGS proteins (such as aberrant expression of RGS proteins) is closely associated with pathologies of many diseases such as cancer. In this review, we summarize the molecular mechanisms governing the expression of RGS proteins, and further discuss the relationship of RGS proteins and cancer.