Bossis Guillaume, Melchior Frauke
Department of Biochemie I, University Goettingen, Humboldt Allee 23, 37073 Goettingen, Germany.
Mol Cell. 2006 Feb 3;21(3):349-57. doi: 10.1016/j.molcel.2005.12.019.
Posttranslational modification with small ubiquitin-related modifier (SUMO) has emerged as a central regulatory mechanism of protein function. However, little is known about the regulation of sumoylation itself. It has been reported that it is increased after exposure to various stresses including strong oxidative stress. Conversely, we report that ROS (reactive oxygen species), at low concentrations, result in the rapid disappearance of most SUMO conjugates, including those of key transcription factors. This is due to direct and reversible inhibition of SUMO conjugating enzymes through the formation of (a) disulfide bond(s) involving the catalytic cysteines of the SUMO E1 subunit Uba2 and the E2-conjugating enzyme Ubc9. The same phenomenon is also observed in a physiological scenario of endogenous ROS production, the respiratory burst in macrophages. Thus, our findings add SUMO conjugating enzymes to the small list of specific direct effectors of H(2)O(2) and implicate ROS as key regulators of the sumoylation-desumoylation equilibrium.
用小泛素相关修饰物（SUMO）进行的翻译后修饰已成为蛋白质功能的核心调节机制。然而，关于SUMO化本身的调节知之甚少。据报道，在暴露于包括强氧化应激在内的各种应激后，SUMO化会增加。相反，我们报告低浓度的活性氧（ROS）会导致大多数SUMO缀合物迅速消失，包括关键转录因子的SUMO缀合物。这是由于通过形成涉及SUMO E1亚基Uba2和E2缀合酶Ubc9的催化半胱氨酸的二硫键，直接且可逆地抑制了SUMO缀合酶。在内源性ROS产生的生理场景即巨噬细胞的呼吸爆发中也观察到相同现象。因此，我们的发现将SUMO缀合酶添加到H2O2的特定直接效应器的小列表中，并表明ROS是SUMO化-去SUMO化平衡的关键调节因子。
