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Increased expression of p62 in expanded polyglutamine‐expressing cells and its association with polyglutamine inclusions
Author(s) -
Nagaoka Utako,
Kim Ken,
Jaihar Ranjan,
Doi Hiroshi,
Maruyama Mieko,
Mitsui Kenichi,
Oyama Fumitaka,
Nukiobuyuki
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02692.x
Subject(s) - aggresome , huntingtin , ubiquitin , biology , exon , polyglutamine tract , huntingtin protein , inclusion bodies , microbiology and biotechnology , hek 293 cells , spinocerebellar ataxia , transgene , gene , chemistry , genetics , recombinant dna , mutant
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.