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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1999-1-29
|
| pubmed:abstractText |
Autosomal dominant spinocerebellar ataxias (SCA) form a group of clinically and genetically heterogeneous neurodegenerative disorders. The defect responsible for SCA3/Machado-Joseph disease (MJD) has been identified as an unstable and expanded (CAG)n trinucleotide repeat in the coding region of a novel gene of unknown function. The MJD1 gene product, ataxin-3, exists in several isoforms. We generated polyclonal antisera against an alternate carboxy terminus of ataxin-3. This isoform, ataxin-3c, is expressed as a protein of approximately 42 kDa in normal individuals but is significantly enlarged in affected patients confirming that the CAG repeat is part of the ataxin-3c isoform and is translated into a polyglutamine stretch, a feature common to all known CAG repeat disorders. Ataxin-3 like immunoreactivity was observed in all human brain regions and peripheral organs studied. In neuronal cells of control individuals, ataxin-3c was expressed cytoplasmatically and had a somatodendritic and axonal distribution. In SCA3 patients, however, C-terminal ataxin-3c antibodies as well as anti-ataxin-3 monoclonal antibodies (1 H9) and anti-ubiquitin antibodies detected intranuclear inclusions (NIs) in neuronal cells of affected brain regions. A monoclonal antibody, 2B6, directed against an internal part of the protein, barely detected these NIs implying proteolytic cleavage of ataxin-3 prior to its transport into the nucleus. These findings provide evidence that the alternate isoform of ataxin-3 is involved in the pathogenesis of SCA3/MJD. Intranuclear protein aggregates appear as a common feature of neurodegenerative polyglutamine disorders.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATXN3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Atxn3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
1015-6305
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
8
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
669-79
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9804376-Amino Acid Sequence,
pubmed-meshheading:9804376-Animals,
pubmed-meshheading:9804376-Blotting, Western,
pubmed-meshheading:9804376-Brain,
pubmed-meshheading:9804376-Brain Chemistry,
pubmed-meshheading:9804376-Brain Neoplasms,
pubmed-meshheading:9804376-Cell Line,
pubmed-meshheading:9804376-Cell Nucleus,
pubmed-meshheading:9804376-DNA,
pubmed-meshheading:9804376-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:9804376-Fluorescent Antibody Technique,
pubmed-meshheading:9804376-Humans,
pubmed-meshheading:9804376-Molecular Sequence Data,
pubmed-meshheading:9804376-Nerve Tissue Proteins,
pubmed-meshheading:9804376-Neuroblastoma,
pubmed-meshheading:9804376-Neurons,
pubmed-meshheading:9804376-Nuclear Proteins,
pubmed-meshheading:9804376-Rats,
pubmed-meshheading:9804376-Repressor Proteins,
pubmed-meshheading:9804376-Spinocerebellar Degenerations
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
An isoform of ataxin-3 accumulates in the nucleus of neuronal cells in affected brain regions of SCA3 patients.
|
| pubmed:affiliation |
Molecular Human Genetics, Ruhr-University, Bochum, Germany.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|