Spinocerebellar ataxia type 35 (SCA35)-associated transglutaminase 6 mutants sensitize cells to apoptosis.
Biochem Biophys Res Commun
; 430(2): 780-6, 2013 Jan 11.
Article
en En
| MEDLINE
| ID: mdl-23206699
ABSTRACT
Spinocerebellar ataxia type 35 (SCA35) is an autosomal dominant neurodegenerative disorder. In our previous study, using exome sequencing and linkage analysis, two missense mutations of the transglutaminase 6 (TGM6) gene were identified as causative for SCA35. TGM6 encodes transglutaminase 6 (TG6), a member of the transglutaminase family of enzymes that catalyze the formation of a covalent bond between a free amine group and the γ-carboxamide group of protein- or peptide-bound glutamine. However, the precise role of TG6 in contributing to SCA35 remains unclear. In this study, we analyzed the subcellular distribution, expression and in vitro activity of two missense mutations of TG6 (D327G, L517W) and found that both mutants exhibited decreased transglutaminase activity and stability. Furthermore, overexpressing the TG6 mutants sensitized cells to staurosporine-induced apoptosis by increasing the activity of caspases. We propose that the pro-apoptotic role of these mutants might underlie the pathogenesis of SCA35.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transglutaminasas
/
Apoptosis
/
Ataxias Espinocerebelosas
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2013
Tipo del documento:
Article
País de afiliación:
China