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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-3-4
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pubmed:abstractText |
Huntington's disease (HD) is an inherited neurodegenerative disorder. Here we demonstrate that expression of arfaptin 2/POR1 (partner of Rac1) in cultured cells induces the formation of pericentriolar and nuclear aggregates, which morphologically resemble mutant huntingtin aggregates characteristic of HD. Endogenous arfaptin 2 localizes to aggregates induced by expression of an abnormal amino-terminal fragment of huntingtin that contains polyglutamine (polyQ) expansions. A dominant inhibitory mutant of arfaptin 2 inhibits aggregation of mutant huntingtin, but not in the presence of proteasome inhibitors. Using cell-free biochemical assays, we show that arfaptin 2 inhibits proteasome activity. Finally, we show that expression of arfaptin 2 is increased at sites of neurodegeneration and the protein localizes to huntingtin aggregates in HD transgenic mouse brains. Our data suggest that arfaptin 2 is involved in regulating huntingtin protein aggregation, possibly by impairing proteasome function.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ARFIP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hdh protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hdh protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1465-7392
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
240-5
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11854752-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:11854752-Animals,
pubmed-meshheading:11854752-Brain,
pubmed-meshheading:11854752-CHO Cells,
pubmed-meshheading:11854752-Carrier Proteins,
pubmed-meshheading:11854752-Cricetinae,
pubmed-meshheading:11854752-Humans,
pubmed-meshheading:11854752-Huntington Disease,
pubmed-meshheading:11854752-Macromolecular Substances,
pubmed-meshheading:11854752-Mice,
pubmed-meshheading:11854752-Mice, Inbred C57BL,
pubmed-meshheading:11854752-Mice, Inbred CBA,
pubmed-meshheading:11854752-Mice, Transgenic,
pubmed-meshheading:11854752-Microscopy, Immunoelectron,
pubmed-meshheading:11854752-Mutation,
pubmed-meshheading:11854752-Nerve Degeneration,
pubmed-meshheading:11854752-Nerve Tissue Proteins,
pubmed-meshheading:11854752-Nuclear Proteins,
pubmed-meshheading:11854752-PC12 Cells,
pubmed-meshheading:11854752-Rats,
pubmed-meshheading:11854752-Recombinant Fusion Proteins,
pubmed-meshheading:11854752-Transfection
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pubmed:year |
2002
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pubmed:articleTitle |
Arfaptin 2 regulates the aggregation of mutant huntingtin protein.
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pubmed:affiliation |
Division of Tumor Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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