Mahogunin ring finger 1 suppresses misfolded polyglutamine aggregation and cytotoxicity.
Biochim Biophys Acta
; 1842(9): 1472-84, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24769000
ABSTRACT
Polyglutamine diseases are a family of inherited neurodegenerative diseases caused by the expansion of CAG repeats within the coding region of target genes. Still the mechanism(s) by which polyglutamine proteins are ubiquitinated and degraded remains obscure. Here, for the first time, we demonstrate that Mahogunin 21 ring finger 1 E3 ubiquitin protein ligase is depleted in cells that express expanded-polyglutamine proteins. MGRN1 co-immunoprecipitates with expanded-polyglutamine huntingtin and ataxin-3 proteins. Furthermore, we show that MGRN1 is predominantly colocalized and recruits with polyglutamine aggregates in both cellular and transgenic mouse models. Finally, we demonstrate that the partial depletion of MGRN1 increases the rate of aggregate formation and cell death, whereas the overexpression of MGRN1 reduces the frequency of aggregate formation and provides cytoprotection against polyglutamine-induced proteotoxicity. These observations suggest that stimulating the activity of MGRN1 ubiquitin ligase might be a potential therapeutic target to eliminate the cytotoxic threat in polyglutamine diseases.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Dobramento de Proteína
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Apoptose
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Ubiquitina
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Ubiquitina-Proteína Ligases
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Índia