SUMO-1 modification increases human SOD1 stability and aggregation
SUMO-1 modification increases human SOD1 stability and aggregation
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DOI：
10.1016/j.bbrc.2006.06.092
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发表时间：
2006-08-25
影响因子：
3.1
通讯作者：
Wang, Guanghui
中科院分区：
文献类型：
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作者：
Fei, Erkang;Jia, Nali;Wang, Guanghui
编码铜锌超氧化物歧化酶（SOD1）的基因突变导致大约20%的家族性肌萎缩性侧索硬化症（FALS），其特征是运动神经元的选择性丧失。突变SOD1在FALS患者的组织中形成包涵体。然而，SOD1突变体积累的确切机制尚不清楚。我们发现人类SOD1是由SUMO-1修饰的底物。在SOD1的SUMO一致序列中赖氨酸75向精氨酸的转化完全消除了SOD1的SUMO化。我们进一步发现，sumo - 1修饰在野生型和突变型SOD1上都增加了SOD1的稳态水平和聚集。此外，SUMO-1共定位于SOD1形成的聚集体上。这些结果提示，SUMO-1修饰赖氨酸75可能参与调节SOD I的稳定性及其聚集过程。因此，我们的研究结果表明SOD1的sumoylation可能参与了与SOD1突变相关的FALS的发病机制。(c) 2006爱思唯尔公司版权所有。
The mutations in the gene encoding copper-zinc superoxide dismutase (SOD1) cause approximately 20% cases of familial amyotrophic lateral sclerosis (FALS), characterized by selective loss of motor neurons. Mutant SOD1 forms inclusions in tissues from FALS patients. However, the precise mechanism of the accumulation of mutant SOD1 remains unclear. Here we show that human SOD1 is a substrate modified by SUMO-1. A conversion of lysine 75 to an arginine within a SUMO consensus sequence in SOD1 completely abolishes SOD1 sumoylation. We further show that SUMO-I modification, on both wild-type and mutant SOD1, increases SOD1 steady state level and aggregation. Moreover, SUMO-1 co-localizes onto the aggregates formed by SOD1. These findings imply that SUMO-1 modification on lysine 75 may participate in regulating SOD I stability and its aggregation process. Thus, our results suggest that sumoylation of SOD1 may be involved in the pathogenesis of FALS associated with mutant SOD1. (c) 2006 Elsevier Inc. All rights reserved.