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

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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

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Title: 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
Author: Takano, Hiroki; Gusella, James Francis

Note: Order does not necessarily reflect citation order of authors.

Citation: Takano, 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.
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Abstract: Background: 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.
Published Version: doi:10.1186/1471-2202-3-15
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC137586/pdf/
http://www.biomedcentral.com/1471-2202/3/15
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4632529
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