Protein phosphatase magnesium-dependent 1 gamma (PPM1G)

Protein phosphatase magnesium-dependent 1 gamma (PPM1G) is a member of the PP2C family of serine/threonine phosphatases that require Mg2+ or Mn2+ ions for activity[1][3]. It is widely expressed in human tissues and predominantly localized in the nucleus but also found in the cytoplasm. PPM1G regulates multiple cellular processes, including cell cycle progression (dephosphorylating regulatory proteins such as CDK1, RB, p21, and p27), RNA splicing (through dynamic association with the spliceosome and splicing factors like SRSF3), mRNA processing, protein synthesis (via 4E-BP1 and eIF4E complex), DNA damage response (ATM–USP7S–p53 pathway), and cell adhesion (acting with B56δ to control α-catenin and adherens junctions)[1][3][5]. Elevated expression or altered activity of PPM1G is linked to cancer progression, especially hepatocellular carcinoma, where it promotes proliferation, invasion, and poor clinical outcomes. It also plays roles in immune regulation by modulating innate signaling pathways[4]. Inhibitors or modulators of PPM1G, while not currently in clinical use, would theoretically alter the phosphorylation state of a range of target proteins, impacting cancer growth, cell migration, or immune function.

Other names

Protein phosphatase 1GPPM1GPPM1CPP2C-gammaPP2CGPP2CgammaProtein phosphatase 1CProtein phosphatase 2C isoform gammaProtein phosphatase magnesium-dependent 1 gammaPP2C, gammaprotein phosphatase 2C, gamma isoformPP2CGAMMAPPP2CGprotein phosphatase 1Gprotein phosphatase 1Cprotein phosphatase magnesium-dependent 1 gamma

Drugs would act by inhibiting or modulating the phosphatase activity of PPM1G, thereby impacting dephosphorylation of serine/threonine residues on substrate proteins[1][3].