SUMO1 attenuates stress-induced ROS generation by inhibiting NADPH oxidase 2

Small ubiquitin-like modifier 1 (SUMO1) is a member of the superfamily of ubiquitin-like proteins. Despite its structural similarity with ubiquitin, SUMO1 does not seem to play any role in protein degradation and its precise biological function is poorly understood. During our studies on heat-shock responses, we found that heat-shock stress increased SUMO1 conjugation in a dose-dependent manner. Intriguingly, SUMO1 conjugation resulted in decrease of intracellular ROS generation and protection cells from death under heat-shock stress. We showed that NADPH oxidase 2 (NOX2) is a target protein of sumoylation by SUMO1 using immunoprecipitation and is colocalized with SUMO1 at plasma membrane. Additionally, we demonstrated that the attenuation in intracellular ROS generation resulted from inhibition of NADPH oxidase complex (NOX) activity. These results suggested that SUMO1 plays an important role in modulation of NOX activity required for ROS generation.

► Sumoylation by SUMO1 is increased in a dose-dependent manner and has an inhibitory effect on ROS generation upon heat-shock.
► SUMO1 decreases JNK and p38 activities, downstream of intracellular ROS signaling molecule, and increases cell viability response to heat-shock.
► NOX2, a major ROS generator, is sumoylated by SUMO1 at plasma membrane and sumoylation modulates NOX activity negatively.