SUMO3 modification accelerates the aggregation of ALS-Linked SOD1 mutants

Takako Niikura, Yoshiko Kita, Yoichiro Abe

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Article numbere101080
JournalPLoS One
Volume9
Issue number6
DOIs
Publication statusPublished - 2014 Jun 27

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Amyotrophic Lateral Sclerosis
Superoxide Dismutase
superoxide dismutase
Mutant Proteins
Agglomeration
Lysine
mutants
lysine
protein aggregates
proteins
Sumoylation
Protein Stability
Ubiquitin
modifiers (genes)
ubiquitin
Proteins
Cells
Cell Line
pathogenesis
Mutation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

SUMO3 modification accelerates the aggregation of ALS-Linked SOD1 mutants. / Niikura, Takako; Kita, Yoshiko; Abe, Yoichiro.

In: PLoS One, Vol. 9, No. 6, e101080, 27.06.2014.

Research output: Contribution to journalArticle

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