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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2005-8-26
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pubmed:abstractText |
Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by an expanded glutamine tract in human Ataxin-1 (hAtx-1). The expansion stabilizes hAtx-1, leading to its accumulation. To understand how stabilized hAtx-1 induces selective neuronal degeneration, we studied Drosophila Atx-1 (dAtx-1), which has a conserved AXH domain but lacks a polyglutamine tract. Overexpression of hAtx-1 in fruit flies produces phenotypes similar to those of dAtx-1 but different from the polyglutamine peptide alone. We show that the Drosophila and mammalian transcription factors Senseless/Gfi-1 interact with Atx-1's AXH domain. In flies, overexpression of Atx-1 inhibits sensory-organ development by decreasing Senseless protein. Similarly, overexpression of wild-type and glutamine-expanded hAtx-1 reduces Gfi-1 levels in Purkinje cells. Deletion of the AXH domain abolishes the effects of glutamine-expanded hAtx-1 on Senseless/Gfi-1. Interestingly, loss of Gfi-1 mimics SCA1 phenotypes in Purkinje cells. These results indicate that the Atx-1/Gfi-1 interaction contributes to the selective Purkinje cell degeneration in SCA1.
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pubmed:grant |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0092-8674
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pubmed:author |
pubmed-author:BellenHugo JHJ,
pubmed-author:BotasJuanJ,
pubmed-author:ChenHung-KaiHK,
pubmed-author:Jafar-NejadHamedH,
pubmed-author:OrrHarry THT,
pubmed-author:PatelAkash JAJ,
pubmed-author:RoseMatthew FMF,
pubmed-author:SunYalingY,
pubmed-author:TsudaHiroshiH,
pubmed-author:VenkenKoen J TKJ,
pubmed-author:ZoghbiHuda YHY
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
122
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
633-44
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16122429-Animals,
pubmed-meshheading:16122429-Cells, Cultured,
pubmed-meshheading:16122429-Cerebellum,
pubmed-meshheading:16122429-DNA-Binding Proteins,
pubmed-meshheading:16122429-Down-Regulation,
pubmed-meshheading:16122429-Drosophila Proteins,
pubmed-meshheading:16122429-Drosophila melanogaster,
pubmed-meshheading:16122429-Mice,
pubmed-meshheading:16122429-Mice, Transgenic,
pubmed-meshheading:16122429-Nerve Degeneration,
pubmed-meshheading:16122429-Nerve Tissue Proteins,
pubmed-meshheading:16122429-Nervous System,
pubmed-meshheading:16122429-Nervous System Malformations,
pubmed-meshheading:16122429-Nuclear Proteins,
pubmed-meshheading:16122429-Protein Structure, Tertiary,
pubmed-meshheading:16122429-Purkinje Cells,
pubmed-meshheading:16122429-Spinocerebellar Ataxias,
pubmed-meshheading:16122429-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins.
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pubmed:affiliation |
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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