title: SUMO3 modification accelerates the aggregation of ALS-linked SOD1 mutants.
abstract: Mutations in superoxide dismutase 1 (SOD1) are a major cause of familial amyotrophic lateral sclerosis (ALS), whereby the mutant proteins misfold and aggregate to form intracellular inclusions. We report that both small ubiquitin-like modifier (SUMO) 1 and SUMO2/3 modify ALS-linked SOD1 mutant proteins at lysine 75 in a motoneuronal cell line, the cell type affected in ALS. In these cells, SUMO1 modification occurred on both lysine 75 and lysine 9 of SOD1, and modification of ALS-linked SOD1 mutant proteins by SUMO3, rather than by SUMO1, significantly increased the stability of the proteins and accelerated intracellular aggregate formation. These findings suggest the contribution of sumoylation, particularly by SUMO3, to the protein aggregation process underlying the pathogenesis of ALS.
authors: Department of Information and Communication Sciences, Faculty of Science and Technology, Sophia University, Tokyo, Japan.
authors: Takako
authors: T
authors: Niikura
authors: Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
authors: Yoshiko
authors: Y
authors: Kita
authors: Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
authors: Yoichiro
authors: Y
authors: Abe
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D066263:Protein Aggregation, Pathological / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D025842:SUMO-1 Protein / Q000378:metabolism; D058207:Sumoylation; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: C000606290:SOD1 protein, human; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C492189:SUMO3 protein, human; D014452:Ubiquitins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1