Role of TMX2 on maintaining nucleocytoplasmic gradient of Ran GTPase under oxidative stress conditions

Abstract

Impairment of the protein nuclear transport system accompanying disruption of the nucleocytoplasmic gradient of Ran GTPase by oxidative stress is one of the causes of cellular senescence. In this study, we found that Thioredoxin-related transmembrane protein 2 (TMX2) regulate the nuclear Ran levels and importin-β-mediated transport of cargo protein. The cysteine 112 residue of Ran was important in its regulation by TMX2 and in the reduced nuclear Ran levels by oxidative stress. These results suggest that nuclear Ran levels are regulated by its redox state via TMX2.