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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-9-22
pubmed:abstractText
Analysis of protein-protein interactions (PPIs) is a valuable approach for characterizing proteins of unknown function. Here, we have developed a strategy combining library and matrix yeast two-hybrid screens to generate a highly connected PPI network for Huntington's disease (HD). The network contains 186 PPIs among 35 bait and 51 prey proteins. It revealed 165 new potential interactions, 32 of which were confirmed by independent binding experiments. The network also permitted the functional annotation of 16 uncharacterized proteins and facilitated the discovery of GIT1, a G protein-coupled receptor kinase-interacting protein, which enhances huntingtin aggregation by recruitment of the protein into membranous vesicles. Coimmunoprecipitations and immunofluorescence studies revealed that GIT1 and huntingtin associate in mammalian cells under physiological conditions. Moreover, GIT1 localizes to neuronal inclusions, and is selectively cleaved in HD brains, indicating that its distribution and function is altered during disease pathogenesis.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/GIT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/GTPase-Activating Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Git1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Git1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione, 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/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Proline, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1097-2765
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Cell Press
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
853-65
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15383276-Humans, pubmed-meshheading:15383276-Animals, pubmed-meshheading:15383276-Mice, pubmed-meshheading:15383276-Rats, pubmed-meshheading:15383276-Proline, pubmed-meshheading:15383276-Glutathione, pubmed-meshheading:15383276-Huntington Disease, pubmed-meshheading:15383276-Precipitin Tests, pubmed-meshheading:15383276-Nerve Tissue Proteins, pubmed-meshheading:15383276-Amino Acid Sequence, pubmed-meshheading:15383276-Protein Binding, pubmed-meshheading:15383276-Tissue Distribution, pubmed-meshheading:15383276-Binding Sites, pubmed-meshheading:15383276-Nuclear Proteins, pubmed-meshheading:15383276-Cercopithecus aethiops, pubmed-meshheading:15383276-Protein Structure, Tertiary, pubmed-meshheading:15383276-Phosphoproteins, pubmed-meshheading:15383276-Antibodies, Monoclonal, pubmed-meshheading:15383276-Two-Hybrid System Techniques, pubmed-meshheading:15383276-Recombinant Fusion Proteins, pubmed-meshheading:15383276-COS Cells, pubmed-meshheading:15383276-Adaptor Proteins, Signal Transducing, pubmed-meshheading:15383276-Cell Cycle Proteins, pubmed-meshheading:15383276-Mice, Transgenic, pubmed-meshheading:15383276-PC12 Cells, pubmed-meshheading:15383276-GTPase-Activating Proteins, pubmed-meshheading:15383276-RNA Interference
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