Regulator of G-protein signaling 17 (RGS17)

Regulator of G-protein signaling 17 (RGS17) is a member of the RZ subfamily of the regulator of G-protein signaling (RGS) proteins, characterized by a conserved RGS domain and a cysteine-rich region. RGS17 acts as a GTPase-activating protein (GAP), binding to activated, GTP-bound G alpha subunits of G proteins (notably Gαi1-3, Gαo, and Gαz), and accelerates their inactivation by increasing the rate of GTP hydrolysis. This terminates GPCR-mediated signaling, playing a key role in opioid receptor desensitization, tolerance development, and cellular signal homeostasis[1][2][3]. RGS17 is overexpressed in several cancers (including lung and prostate), supports tumor cell proliferation via cAMP/CREB pathway modulation, and is implicated in the development of opioid tolerance and cisplatin-induced hearing loss. Research is ongoing to develop small-molecule inhibitors targeting RGS17 for cancer and ototoxicity therapies, with gene and protein expression being explored as biomarkers for disease risk and treatment efficacy[1][4][5][7].

Other names

RGSZ2RGS-17hRGS17Regulator of G protein signaling 17Regulator of G-protein signaling 17

Negative modulation of GPCR signaling by accelerating GTP hydrolysis of G alpha subunits. Disruption or inhibition of RGS17 can prolong GPCR signal duration (theoretical for drug targeting). Inhibition of RGS17 is hypothesized to suppress oncogenic signaling in cancers by restoring GPCR-mediated growth suppression.