ABSTRACT
S-Glutathionylation is a reversible PTM of cysteine residues, resulting in a subsequent increase in molecular mass of ~305.6d and a net increase in negative charge. While canonical phosphorylation and dephosphorylation pathways are cyclical, numerous kinases and phosphatases are secondarily regulated by S-glutathionylation, providing layered control of phosphorus-based signaling by sulfur, following stimuli that cause homeostatic changes in reactive oxygen species (ROS)/reactive nitrogen species. Local production of ROS may also favor catalysis of thiyl radical scavenging or protein S-glutathionylation by Grx. At the genetic level, the glutathione S-transferase P (GSTP) gene demonstrates several distinct, but ultimately overlapping mechanisms of pleiotropy. For example, the gene product interacts with multiple other proteins, mutations generally impact the resulting phenotype in various ways, and resultant phenotypes alter various measures of organismal fitness. The characteristic bone marrow phenotype of the GSTP knockout mouse is consistent with regulatory control through S-glutathionylation of certain key proteins.
