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- Publisher
- Oxford University Press
- Copyright
- Copyright © 2015 Oxford University Press
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- DOI
- 10.1093/hmg/9.14.2197
- Publisher site
- See Article on Publisher Site
Abstract
Spinal and bulbar muscular atrophy (SBMA) is one of eight inherited neurodegenerative diseases known to be caused by CAG repeat expansion. The expansion results in an expanded polyglutamine tract, which likely confers a novel, toxic function to the affected protein. Cell culture and transgenic mouse studies have implicated the nucleus as a site for pathogenesis, suggesting that a critical nuclear factor or process is disrupted by the polyglutamine expansion. In this report we present evidence that CREB-binding protein (CBP), a transcriptional co-activator that orchestrates nuclear response to a variety of cell signaling cascades, is incorporated into nuclear inclusions formed by polyglutamine-containing proteins in cultured cells, transgenic mice and tissue from patients with SBMA. We also show CBP incorporation into nuclear inclusions formed in a cell culture model of another polyglutamine disease, spinocerebellar ataxia type 3. We present evidence that soluble levels of CBP are reduced in cells expressing expanded polyglutamine despite increased levels of CBP mRNA. Finally, we demonstrate that over-expression of CBP rescues cells from polyglutamine-mediated toxicity in neuronal cell culture. These data support a CBP-sequestration model of polyglutamine expansion disease. Received 2 June 2000; Revised and Accepted 10 July 2000. « Previous | Next Article » Table of Contents This Article Hum. Mol. Genet. (2000) 9 (14): 2197-2202. doi: 10.1093/hmg/9.14.2197 » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Report Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by McCampbell, A. Articles by Fischbeck, K. H. Search for related content PubMed PubMed citation Articles by McCampbell, A. Articles by Taylor, J. P. Articles by Taye, A. A. Articles by Robitschek, J. Articles by Li, M. Articles by Walcott, J. Articles by Merry, D. Articles by Chai, Y. Articles by Paulson, H. Articles by Sobue, G. Articles by Fischbeck, K. H. 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Journal
Human Molecular Genetics – Oxford University Press
Published: Sep 1, 2000