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Increased expression of p62 in expanded polyglutamine-expressing cells and its association with polyglutamine inclusions.
- Source :
-
Journal of neurochemistry [J Neurochem] 2004 Oct; Vol. 91 (1), pp. 57-68. - Publication Year :
- 2004
-
Abstract
- Huntington's disease is a progressive neurodegenerative disorder that is associated with a CAG repeat expansion in the gene encoding huntingtin. We found that a 60-kDa protein was increased in Neuro2a cells expressing the N-terminal portion of huntingtin with expanded polyglutamine. We purified this protein, and, using mass spectrometry, identified it as p62, an ubiquitin-associated domain-containing protein. A specific p62 antibody stained the ubiquitylated polyQ inclusions in expanded polyglutamine-expressing cells, as well as in the brain of the huntingtin exon 1 transgenic mice. Furthermore, the level of p62 protein and mRNA was increased in expanded polyglutamine-expressing cells. We also found that p62 formed aggresome-like inclusions when p62 was increased in normal Neuro2a cells by a proteasome inhibitor. Knock-down of p62 does not affect the formation of aggresomes or polyglutamine inclusions, suggesting that p62 is recruited to the aggresome or inclusions secondary to their formation. These results suggest that p62 may play important roles as a responsive protein to a polyglutamine-induced stress rather than as a cross-linker between ubiquitylated proteins.
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Brain cytology
Brain metabolism
Carrier Proteins immunology
Cell Count methods
Cell Fractionation methods
Cell Line, Tumor
Cell Nucleus metabolism
Chromatography, High Pressure Liquid methods
Cysteine Proteinase Inhibitors pharmacology
DNA-Binding Proteins
Drug Interactions
Exons genetics
Fluorescent Antibody Technique methods
Green Fluorescent Proteins metabolism
Huntingtin Protein
Immunoblotting methods
Immunoprecipitation methods
Inclusion Bodies chemistry
Indoles metabolism
Leupeptins pharmacology
Male
Mass Spectrometry methods
Mice
Mice, Knockout
Nerve Tissue Proteins genetics
Neuroblastoma
Neurons cytology
Neurons metabolism
Nocodazole pharmacology
Nuclear Proteins genetics
RNA Interference physiology
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction methods
Sequence Analysis, Protein methods
Time Factors
Transcription Factor TFIIH
Transcription Factors chemistry
Transfection methods
Ubiquitin metabolism
Carrier Proteins metabolism
Gene Expression Regulation physiology
Inclusion Bodies metabolism
Peptides metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3042
- Volume :
- 91
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15379887
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2004.02692.x