Effects of DJ-1 mutations and polymorphisms on protein stability and subcellular localization.
Brain Res Mol Brain Res
; 134(1): 76-83, 2005 Mar 24.
Article
en En
| MEDLINE
| ID: mdl-15790532
ABSTRACT
Mutations in the DJ-1 gene are associated with recessive, early onset Parkinson's disease (PD). We reported previously that one of the point mutations, L166P, destabilizes the protein and thus produces an effective knockout of the gene. Here, we have expanded this analysis to include a series of mutations and polymorphisms identified throughout the gene. The M26I point mutation was also unstable, although the effect was not as dramatic as with L166P. Protein levels were rescued in part, but not completely, by proteasome inhibition. Other variants, such as R98Q, were generally stable. We noted that M26I and L166P are both in helical regions near the dimer interface. However, M26I retains the ability to dimerize. We also examined the subcellular localization of DJ-1 and found that most mutations were similar to the wild-type (wt) protein in that a few cells showed mitochondrial staining. However, in all cases, the proportion of cells with mitochondrial DJ-1 staining was increased in oxidative conditions, suggesting that oxidation promotes the mitochondrial localization of DJ-1.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Acetilcisteína
/
Mutación Puntual
/
Proteínas Oncogénicas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Brain Res Mol Brain Res
Asunto de la revista:
BIOLOGIA MOLECULAR
/
CEREBRO
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos