Rhes, a Striatal Specific Protein, Mediates Mutant-Huntingtin Cytotoxicity
- 5 June 2009
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 324 (5932) , 1327-1330
- https://doi.org/10.1126/science.1172871
Abstract
Huntington’s disease (HD) is caused by a polyglutamine repeat in the protein huntingtin (Htt) with mutant Htt (mHtt) expressed throughout the body and similarly in all brain regions. Yet, HD neuropathology is largely restricted to the corpus striatum. We report that the small guanine nucleotide–binding protein Rhes, which is localized very selectively to the striatum, binds physiologically to mHtt. Using cultured cells, we found Rhes induces sumoylation of mHtt, which leads to cytotoxicity. Thus, Rhes-mHtt interactions can account for the localized neuropathology of HD.Keywords
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