SUMO-1 modification increases human SOD1 stability and aggregation

• DOI: 10.1016/j.bbrc.2006.06.092
• Publication Date: 2006-06-24T11:27:02Z
• Authors: Erkang Fei; Nali Jia; Ming Yan; Zheng Ying; Qiang Sun; Hongfeng Wang; Tao Zhang; Xiaochuan Ma; Husheng Ding; Xuebiao Yao; Yunyu Shi; Guanghui Wang
• Keywords: 0301 basic medicine; 0303 health sciences; Protein Conformation; Superoxide Dismutase; Lysine; Green Fluorescent Proteins; Immunoblotting; SUMO-1 Protein; Transfection; Cell Line; 03 medical and health sciences; Enzyme Stability; Mutation; Small Ubiquitin-Related Modifier Proteins; Humans; Immunoprecipitation; Ubiquitins; Protein Binding

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-1 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 SOD1 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.