Figure 6. Model demonstrating that oxidative and nitrosative stress block the sumoylation pathway through different mechanisms.

Top: In a normal redox environment, Ubc9 conjugates SUMO to the substrate with the help of E3 ligase. Middle: Oxidative stress leads to formation of a disulfide bond between the E1 subunit Uba2 and the E2 subunit Ubc9, resulting in inactivation of both E1 and E2 enzymes. Below: Under nitrosative stress, both Ubc9 and Pias3 are S-nitrosated. Whereas S-nitrosation of Ubc9 cannot interfere with its catalytic activity, S-nitrosation of Pias3 facilitates its degradation by promoting its interplay with Ub E3 ligase Trim32, thereby resulting in decrease of SUMO conjugating efficiency. Su, SUMO; S, substrate protein.