Abstract
Post-translational modification by SUMO was proposed to modulate the pathogenesis of several neurodegenerative diseases. Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disease caused by polyQ-expanded ataxin-3. We have previously shown that ataxin-3 was a new target of SUMOylation in vitro and in vivo. Here we identified that the major SUMO-1 binding site was located on lysine 166. SUMOylation did not influence the subcellular localization, ubiquitination or aggregates formation of mutant-type ataxin-3, but partially increased its stability and the cell apoptosis. Our findings revealed the role of ataxin-3 SUMOylation in SCA3/MJD pathogenesis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Apoptosis
-
Ataxin-3
-
Binding Sites
-
HEK293 Cells
-
Humans
-
Lysine / chemistry
-
Lysine / metabolism
-
Machado-Joseph Disease / metabolism*
-
Machado-Joseph Disease / physiopathology
-
Mutation
-
Nerve Tissue Proteins / metabolism*
-
Nuclear Proteins / metabolism*
-
Peptides / metabolism*
-
Protein Binding
-
Protein Processing, Post-Translational
-
Repressor Proteins / metabolism*
-
SUMO-1 Protein / metabolism*
-
Sumoylation / genetics*
-
Ubiquitination
Substances
-
Nerve Tissue Proteins
-
Nuclear Proteins
-
Peptides
-
Repressor Proteins
-
SUMO-1 Protein
-
polyglutamine
-
ATXN3 protein, human
-
Ataxin-3
-
Lysine
Grants and funding
This work was supported by the National Natural Sciences Foundation of China (No: 30470619, 30971034, 81000543), Distinguished Youth Foundation of Hunan Province (No: 2007JJ1005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.