SUMO3 modification accelerates the aggregation of ALS-linked SOD1 mutants

• Published in: PloS one Vol. 9; no. 6; p. e101080
• Main Authors: Niikura, Takako, Kita, Yoshiko, Abe, Yoichiro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.06.2014; Public Library of Science (PLoS)
• Subjects: Agglomeration; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Biology and life sciences; Cell Line, Tumor; Disease; Enzymes; HEK293 Cells; Humans; Intracellular; Lysine; Medicine and Health Sciences; Motor Neurons - metabolism; Mutants; Mutation; Neurons; Pathogenesis; Protein Aggregation, Pathological - genetics; Protein Aggregation, Pathological - metabolism; Protein interaction; Protein Stability; Proteins; Proteomics; Rodents; Spinal cord; Studies; SUMO protein; SUMO-1 Protein - metabolism; Sumoylation; Superoxide dismutase; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Superoxide Dismutase-1; Ubiquitin; Ubiquitins - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0101080

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.