Regulation of SUMOylation by reversible oxidation of SUMO conjugating enzymes
Regulation of SUMOylation by reversible oxidation of SUMO conjugating enzymes
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DOI：
10.1016/j.molcel.2005.12.019
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发表时间：
2006-02-03
期刊：
影响因子：
16
通讯作者：
Melchior, F
中科院分区：
文献类型：
--
作者：
Bossis, G;Melchior, F
小泛素相关修饰子（small ubiquitin-related modifier， SUMO）的翻译后修饰已成为蛋白质功能的核心调控机制。然而，对sumoylation本身的调控知之甚少。据报道，在暴露于包括强氧化应激在内的各种应激后，它会增加。相反，我们报告说，低浓度的ROS（活性氧）会导致大多数SUMO偶联物迅速消失，包括关键转录因子的偶联物。这是由于通过形成(a)二硫键(s)，涉及SUMO E1亚基Uba2和e2偶联酶Ubc9的催化半胱氨酸，直接和可逆地抑制了SUMO偶联酶。同样的现象也出现在内源性ROS产生的生理情景中，即巨噬细胞的呼吸爆发。因此，我们的研究结果将SUMO偶联酶添加到H2O2的特定直接效应物的小列表中，并暗示ROS是summoylation -去summoylation平衡的关键调节因子。
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 H2O2 and implicate ROS as key regulators of the sumoylation-desumoylation equilibrium.