TY - JOUR
T1 - Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity
AU - Subramaniam, Srinivasa
AU - Sixt, Katherine M.
AU - Barrow, Roxanne
AU - Snyder, Solomon H.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1172871
DO - 10.1126/science.1172871
M3 - Article
C2 - 19498170
AN - SCOPUS:66749167799
SN - 0036-8075
VL - 324
SP - 1327
EP - 1330
JO - Science
JF - Science
IS - 5932
ER -