title: SUMO-1 modification increases human SOD1 stability and aggregation.
abstract: 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.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
authors.forename: Erkang
authors.initials: E
authors.lastname: Fei
authors.forename: Nali
authors.initials: N
authors.lastname: Jia
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ying
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Ma
authors.forename: Husheng
authors.initials: H
authors.lastname: Ding
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
authors.forename: Yunyu
authors.initials: Y
authors.lastname: Shi
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wang
mesh_terms: D002460:Cell Line; D004795:Enzyme Stability; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008239:Lysine / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins; D049452:Green Fluorescent Proteins; D013482:Superoxide Dismutase; D008239:Lysine