Department of Biochemistry and Molecular Cell Biology, Key Laboratory of the Education Ministry for Cell Differentiation and Apoptosis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Biochem J. 2011 Apr 15;435(2):489-98. doi: 10.1042/BJ20101474.
Protein SUMOylation (SUMO is small ubiquitin-related modifier) is a dynamic process that is strictly regulated under physiological and pathological conditions. However, little is known about how various intra- or extra-cellular stimuli regulate expression levels of components in the SUMO system. SUMO isoforms SUMO2 and SUMO3 can rapidly convert to be conjugated in response to a variety of cellular stresses. Owing to the limitations of sequence homology, SUMO2 and SUMO3 cannot be differentiated between and are thus referred to as SUMO2/3. Whether these two isoforms are regulated in distinct manners has never been addressed. In the present paper we report that the expression of SUMO3, but not SUMO2, can be down-regulated at the transcription level by cellular oxidative stress. In the present study, we checked SUMO2 and SUMO3 mRNA levels in cells exposed to various doses of H2O2 and in cells bearing different levels of ROS (reactive oxygen species). We found an inverse relationship between SUMO3 transcription and ROS levels. We characterized a promoter region specific for the mouse Sumo3 gene that is bound by the redox-sensitive transcription factor Sp1 (specificity protein 1) and demonstrated oxidation of Sp1, as well as suppression of Sp1-DNA binding upon oxidative stress. This revealed for the first time that the expression of SUMO2 and SUMO3 is regulated differently by ROS. These findings may enhance our understanding about the regulation of SUMOylation and also shed light on the functions of Sp1.
蛋白质 SUMO 化（SUMO 是一种小泛素相关修饰物）是一个严格受生理和病理条件调节的动态过程。然而，对于各种细胞内或细胞外刺激如何调节 SUMO 系统成分的表达水平，知之甚少。SUMO 同工型 SUMO2 和 SUMO3 可以迅速转化为被共轭，以响应各种细胞应激。由于序列同源性的限制，SUMO2 和 SUMO3 不能区分，因此被称为 SUMO2/3。这两种同工型是否以不同的方式受到调节尚未得到解决。在本文中，我们报告细胞氧化应激可以在转录水平下调 SUMO3 的表达，但不能下调 SUMO2 的表达。在本研究中，我们检查了暴露于不同剂量 H2O2 的细胞和具有不同 ROS（活性氧）水平的细胞中的 SUMO2 和 SUMO3 mRNA 水平。我们发现 SUMO3 转录与 ROS 水平之间存在反比关系。我们对小鼠 Sumo3 基因的启动子区域进行了特征描述，该区域被氧化还原敏感转录因子 Sp1（特异性蛋白 1）结合，并证明了 Sp1 的氧化以及 Sp1-DNA 结合在氧化应激时受到抑制。这首次揭示了 ROS 对 SUMO2 和 SUMO3 的表达有不同的调节作用。这些发现可能增强我们对 SUMO 化调节的理解，并为 Sp1 的功能提供新的认识。
