title: SUMO-1 co-localized with mutant atrophin-1 with expanded polyglutamines accelerates intranuclear aggregation and cell death.
abstract: To investigate the implication of small ubiquitin-related modifier-1 (SUMO-1) in the formation of neuronal intranuclear inclusions in polyglutamine diseases, we examined the localization of SUMO-1 in dentatorubral-pallidoluysian atrophy (DRPLA) brain tissues and PC12 cells expressing truncated atrophin-1 with expanded poly-glutamine stretches. SUMO-1 was co-localized with neuronal intranuclear inclusions in DRPLA brain and the DRPLA model cells, which showed that the aggregates formed by expanded polyglutamine stretches were highly SUMOlylated. In addition, to examine the role of SUMO-1 in nuclear aggregate formation and cell death, either SUMO-1 or DeltaSUMO-1, which is a SUMOlylation defective mutant lacking the C-terminal motif, was co-transfected with atrophin-1 with expanded polyglutamine stretches. Co-transfection of DeltaSUMO-1 decreased number of the cells with nuclear aggregates and consequent apoptosis of PC12 cells, both of which were markedly enhanced by co-transfection of SUMO-1 with atrophin-1 with expanded polyglutamine stretches. These results suggest that SUMO-1 is implicated in the pathogenesis of DRPLA and accelerates aggregate formation and cell death.
authors.affiliation: Division of Neurology, Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Terashima
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kawai
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujitani
authors.forename: Kengo
authors.initials: K
authors.lastname: Maeda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D016716:PC12 Cells; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D051381:Rats; D025842:SUMO-1 Protein / Q000172:deficiency* / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D010455:Peptides; D025842:SUMO-1 Protein; C095278:atrophin-1; C097188:polyglutamine