کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2037371 1072314 2009 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Acetylation Targets Mutant Huntingtin to Autophagosomes for Degradation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
Acetylation Targets Mutant Huntingtin to Autophagosomes for Degradation
چکیده انگلیسی

SummaryHuntington's disease (HD) is an incurable neurodegenerative disease caused by neuronal accumulation of the mutant protein huntingtin. Improving clearance of the mutant protein is expected to prevent cellular dysfunction and neurodegeneration in HD. We report here that such clearance can be achieved by posttranslational modification of the mutant Huntingtin (Htt) by acetylation at lysine residue 444 (K444). Increased acetylation at K444 facilitates trafficking of mutant Htt into autophagosomes, significantly improves clearance of the mutant protein by macroautophagy, and reverses the toxic effects of mutant huntingtin in primary striatal and cortical neurons and in a transgenic C. elegans model of HD. In contrast, mutant Htt that is rendered resistant to acetylation dramatically accumulates and leads to neurodegeneration in cultured neurons and in mouse brain. These studies identify acetylation as a mechanism for removing accumulated protein in HD, and more broadly for actively targeting proteins for degradation by autophagy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 137, Issue 1, 3 April 2009, Pages 60–72
نویسندگان
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