P66Shc Mediates SUMO2-induced Endothelial Dysfunction.

Endothelial cells control vascular function and health. Increased oxidative stress causes vascular endothelial dysfunction and promotes pathologies such as atherosclerosis and hypertension. SUMO2 and p66Shc increase production of reactive oxygen species and cause endothelial dysfunction through unknown mechanisms. We discovered that p66Shc mediates SUMO2-induced ROS production. In the CH2 domain, unique to p66Shc, SUMO2 modifies lysine-81 (K81) a conserved residue essential for SUMO2-induced oxidative activation and mitochondrial translocation of p66Shc and vascular endothelial dysfunction. Thus, the SUMO2-p66Shc axis regulates endothelial function.