Source:http://linkedlifedata.com/resource/pubmed/id/16079151
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
18
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| pubmed:dateCreated |
2005-9-5
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| pubmed:abstractText |
Mutations in Cu/Zn superoxide dismutase (SOD1) cause approximately 20% of familial amyotrophic lateral sclerosis by a toxic gain of function; however, the precise mechanisms remain unclear. Here, we report the identification of HoxB2, a homeodomain-containing transcription factor, as a G93A mutant SOD1 interactive protein in a yeast two-hybrid screen. We show that HoxB2 co-precipitates and co-localizes with mutant SOD1 in neuronal cell lines, as well as in brain and spinal cord of G93A mutant SOD1 transgenic mice. Mutagenesis further shows that this interaction is mediated by the central homeodomain of HoxB2. In motor neuron-like NSC-34 cells, overexpression of HoxB2 or its homeodomain decreases the insolubility of mutant SOD1 and inhibits G93A or G86R mutant SOD1-induced neuronal cell death. In human and mouse tissues, we show that expression of HoxB2 persists in adult spinal cord and is primarily localized in nuclei of motor neurons. In G93A transgenic mice, HoxB2 co-localizes with mutant SOD1 and is redistributed to perikarya and proximal neurites of motor neurons. In addition, there is progressive accumulation of HoxB2 and mutant SOD1 as punctate inclusions in the neuropil surrounding motor neurons. Taken together, our findings demonstrate that interaction of HoxB2 with mutant SOD1 occurs in motor neurons of G93A mutant SOD1 transgenic mice and suggest that this interaction may modulate the neurotoxicity of mutant SOD1.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/HOXB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/superoxide dismutase 1
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0964-6906
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
14
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2629-40
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:16079151-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:16079151-Animals,
pubmed-meshheading:16079151-Apoptosis,
pubmed-meshheading:16079151-Blotting, Western,
pubmed-meshheading:16079151-Cell Line,
pubmed-meshheading:16079151-Fluorescent Antibody Technique,
pubmed-meshheading:16079151-Gene Expression,
pubmed-meshheading:16079151-Homeodomain Proteins,
pubmed-meshheading:16079151-Humans,
pubmed-meshheading:16079151-Immunohistochemistry,
pubmed-meshheading:16079151-Immunoprecipitation,
pubmed-meshheading:16079151-Mice,
pubmed-meshheading:16079151-Mice, Transgenic,
pubmed-meshheading:16079151-Motor Neurons,
pubmed-meshheading:16079151-Mutagenesis, Site-Directed,
pubmed-meshheading:16079151-Mutation,
pubmed-meshheading:16079151-Oligonucleotides,
pubmed-meshheading:16079151-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16079151-Superoxide Dismutase,
pubmed-meshheading:16079151-Transcription Factors,
pubmed-meshheading:16079151-Two-Hybrid System Techniques
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| pubmed:year |
2005
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| pubmed:articleTitle |
HoxB2 binds mutant SOD1 and is altered in transgenic model of ALS.
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| pubmed:affiliation |
Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. wws435jp@mail.med.upenn.edu
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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