title: SUMO-1 interacts with mutant ataxin-1 and colocalizes to its aggregates in Purkinje cells of SCA1 transgenic mice.
abstract: Spinocerebellar ataxia type 1 (SCA1) is one of several progressive neurodegenerative diseases caused by the expanded polyglutamine tract in ataxin-1, the SCA1 gene product. In SCA1 patients and transgenic mice, the affected neuronal cells contain a large ubiquitin-positive aggregate which is derived from the mutant ataxin-1. Small ubiquitin-like modifier-1 (SUMO-1) is one of the most intriguing ubiquitin-like modifiers being conjugated to target proteins and modulating a number of cellular pathways. Recent findings that the aggregates from several neurodegenerative diseases are SUMO-1-positive prompted us to examine the implication of SUMO-1 in SCA1 pathogenesis. In our yeast two-hybrid experiments using mutant ataxin-1 as bait, we identified a SUMO-1 protein that directly binds to ataxin-1 protein. Interestingly, we found that most of the mutant ataxin-1-derived aggregates were SUMO-1-positive both in Purkinje cells of SCA1 transgenic mice and in HeLa cells, but not wild-type ataxin-1 in HeLa cells. In addition, the aggregates in Purkinje cells of SCA1 transgenic mice were positive against both anti-SUMO-1 and anti-ubiquitin antibodies. These results show that the SUMO-1 protein interacts with mutant ataxin-1 and colocalizes with its aggregates which suggests the involvement of the SUMO-1 system in the pathogenesis of SCA1 disease.
authors.affiliation: Department of Biomedical Science, Korea University, Seoul, Korea.
authors.forename: Seongman
authors.initials: S
authors.lastname: Kang
authors.forename: Sunghoi
authors.initials: S
authors.lastname: Hong
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007211:Indoles; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D011689:Purkinje Cells / Q000502:physiology* / Q000648:ultrastructure; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology*; D014162:Transfection / Q000379:methods; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D007211:Indoles; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D025842:SUMO-1 Protein; D025801:Ubiquitin; C007293:DAPI