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Intranuclear Degradation of Polyglutamine Aggregates by the Ubiquitin-Proteasome System
- Source :
- Journal of Biological Chemistry. 284:9796-9803
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
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.
- Subjects :
- Cytoplasm
Proteasome Endopeptidase Complex
Saccharomyces cerevisiae Proteins
Ubiquitin-Protein Ligases
Protein aggregation
Biochemistry
Inclusion bodies
Ubiquitin
medicine
Humans
Molecular Biology
Cells, Cultured
Cell Nucleus
Neurons
biology
Reverse Transcriptase Polymerase Chain Reaction
Protein Synthesis, Post-Translational Modification, and Degradation
Neurodegenerative Diseases
Cell Biology
Cell biology
Kinetics
Cell nucleus
medicine.anatomical_structure
Proteasome
biology.protein
RNA Interference
Peptides
Nucleus
HeLa Cells
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 284
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....4258b26c9732c8064d3da4829d4af580