Role of the ribosomal quality control machinery in nucleocytoplasmic translocation of polyQ-expanded huntingtin exon-1.
Biochem Biophys Res Commun
; 493(1): 708-717, 2017 11 04.
Article
em En
| MEDLINE
| ID: mdl-28864412
ABSTRACT
The subcellular localization of polyQ-expanded huntingtin exon1 (Httex1) modulates polyQ toxicity in models of Huntington's disease. Using genome-wide screens in a yeast model system, we report that the ribosome quality control (RQC) machinery, recently implicated in neurodegeneration, is a key determinant for the nucleocytoplasmic distribution of Httex1-103Q. Deletion of the RQC genes, LTN1 or RQC1, caused the accumulation of Httex1-103Q in the nucleus through a process that required the CAT-tail tagging activity of Rqc2 and transport via the nuclear pore complex. We provide evidence that nuclear accumulation of Httex1-103Q enhances its cytotoxicity, suggesting that the RQC machinery plays an important role in protecting cells against the adverse effects of polyQ expansion proteins.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Ribossomos
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Núcleo Celular
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Éxons
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Proteína Huntingtina
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article