| Autor: |
Miller SLH; Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709., Scappini EL; Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709., O'Bryan J; Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709; Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612. Electronic address: obryanj@uic.edu. |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2007 Mar 30; Vol. 282 (13), pp. 10096-10103. Date of Electronic Publication: 2007 Feb 02. |
| DOI: |
10.1074/jbc.M611151200 |
| Abstrakt: |
Expansion of polyglutamine (polyQ) tracts within proteins underlies a number of neurodegenerative diseases, such as Huntington disease, Kennedy disease, and spinocerebellar ataxias. The resulting mutant proteins are unstable, forming insoluble aggregates that are associated with components of the ubiquitin system, including ubiquitin, ubiquitin-like proteins, and proteins that bind to ubiquitin. Given the presence of these ubiquitin-binding proteins in the insoluble aggregates, we examined whether heterologous expression of short motifs that bind ubiquitin, termed ubiquitin-interacting motifs (UIMs), altered the aggregation of polyQ-expanded huntingtin (Htt), the protein product of the Huntington disease gene. We found that a subset of UIMs associated with mutant Htt. The ability to interact with ubiquitin was necessary, but not sufficient, for interaction with mutant Htt. Furthermore, we found that expression of single, isolated UIMs inhibited aggregation of mutant Htt. These data suggest that isolated UIMs might serve as potential inhibitors of polyQ-aggregation in vivo. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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