Intranuclear degradation of polyglutamine aggregates by the ubiquitin-proteasome system.
J Biol Chem
; 284(15): 9796-803, 2009 Apr 10.
Article
en En
| MEDLINE
| ID: mdl-19218238
ABSTRACT
Huntington disease and its related autosomal-dominant polyglutamine (pQ) neurodegenerative diseases are characterized by intraneuronal accumulation of protein aggregates. Studies on protein aggregates have revealed the importance of the ubiquitin-proteasome system as the front line of protein quality control (PQC) machinery against aberrant proteins. Recently, we have shown that the autophagy-lysosomal system is also involved in cytoplasmic aggregate degradation, but the nucleus lacked this activity. Consequently, the nucleus relies entirely on the ubiquitin-proteasome system for PQC. According to previous studies, nuclear aggregates possess a higher cellular toxicity than do their cytoplasmic counterparts, however degradation kinetics of nuclear aggregates have been poorly understood. Here we show that nuclear ubiquitin ligases San1p and UHRF-2 each enhance nuclear pQ aggregate degradation and rescued pQ-induced cytotoxicity in cultured cells and primary neurons. Moreover, UHRF-2 is associated with nuclear inclusion bodies in vitro and in vivo. Our data suggest that UHRF-2 is an essential molecule for nuclear pQ degradation as a component of nuclear PQC machinery in mammalian cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Núcleo Celular
/
Enfermedades Neurodegenerativas
/
Ubiquitina
/
Complejo de la Endopetidasa Proteasomal
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón