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dc.contributor.authorTakano, Hiroki
dc.contributor.authorGusella, James Francis
dc.date.accessioned2010-12-21T16:12:46Z
dc.date.issued2002
dc.identifier.citationTakano, Hiroki, and James F. Gusella. 2002. The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factor. BMC Neuroscience 3:15.en_US
dc.identifier.issn1471-2202en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4632529
dc.description.abstractBackground: Huntington's disease (HD) pathogenesis is due to an expanded polyglutamine tract in huntingtin, but the specificity of neuronal loss compared with other polyglutamine disorders also implies a role for the protein's unknown inherent function. Huntingtin is moderately conserved, with 10 HEAT repeats reported in its amino- terminal half. HD orthologues are evident in vertebrates and Drosophila, but not in Saccharomyces cerevisiae, Caenorhabditis elegans or Arabidopsis thaliana, a phylogenetic profile similar to the NF-kB/Rel/dorsal family transcription factors, suggesting a potential functional relationship. Results: We initially tested the potential for a relationship between huntingtin and dorsal by overexpression experiments in Drosophila S2 cells. Drosophila huntingtin complexes via its carboxylterminal region with dorsal, and the two enter the nucleus concomitantly, partly in a lipopolysaccharide (LPS)- and Nup88-dependent manner. Similarly, in HeLa cell extracts, human huntingtin co-immunoprecipitates with NF-kB p50 but not with p105. By cross-species comparative analysis, we find that the carboxyl-terminal segment of huntingtin that mediates the association with dorsal possesses numerous HEAT-like sequences related to those in the amino-terminal segment. Thus, Drosophila and vertebrate huntingtins are composed predominantly of 28 to 36 degenerate HEAT-like repeats that span the entire protein. Conclusion: Like other HEAT-repeat filled proteins, huntingtin is made up largely of degenerate HEAT-like sequences, suggesting that it may play a scaffolding role in the formation of particular protein-protein complexes. While many proteins have been implicated in complexes with the amino-terminal region of huntingtin, the NF-kB/Rel/dorsal family transcription factors merit further examination as direct or indirect interactors with huntingtin's carboxyl-terminal segment.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/1471-2202-3-15en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC137586/pdf/en_US
dc.relation.hasversionhttp://www.biomedcentral.com/1471-2202/3/15en_US
dash.licenseLAA
dc.titleThe Predominantly HEAT-Like Motif Structure of Huntingtin and its Association and Coincident Nuclear Entry with Dorsal, an NF-kB/Rel/Dorsal Family Transcription Factoren_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBMC Neuroscienceen_US
dash.depositing.authorGusella, James Francis
dc.date.available2010-12-21T16:12:46Z
dash.affiliation.otherHMS^Geneticsen_US
dc.identifier.doi10.1186/1471-2202-3-15*
dash.contributor.affiliatedGusella, James


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