| Literature DB >> 16492755 |
Byoung-Il Bae1, Makoto R Hara, Matthew B Cascio, Cheryl L Wellington, Michael R Hayden, Christopher A Ross, Hyo Chol Ha, Xiao-Jiang Li, Solomon H Snyder, Akira Sawa.
Abstract
The pathophysiology of Huntington's disease reflects actions of mutant Huntingtin (Htt) (mHtt) protein with polyglutamine repeats, whose N-terminal fragment translocates to the nucleus to elicit neurotoxicity. We establish that the nuclear translocation and associated cytotoxicity of mHtt reflect a ternary complex of mHtt with GAPDH and Siah1, a ubiquitin-E3-ligase. Overexpression of GAPDH or Siah1 enhances nuclear translocation of mHtt and cytotoxicity, whereas GAPDH mutants that cannot bind Siah1 prevent translocation. Depletion of GAPDH or Siah1 by RNA interference diminishes nuclear translocation of mHtt.Entities:
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Year: 2006 PMID： 16492755 PMCID： PMC1413934 DOI： 10.1073/pnas.0511316103
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205