کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1924759 1536313 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cellular toxicity of yeast prion protein Rnq1 can be modulated by N-terminal wild type huntingtin
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Cellular toxicity of yeast prion protein Rnq1 can be modulated by N-terminal wild type huntingtin
چکیده انگلیسی


• Yeast prion protein Rnq1p forms intracellular amyloid aggregates.
• Presence of N-terminal wild-type huntingtin fragment solubilizes Rnq1p.
• Increased solubility reduces oxidative stress and increases cell survival.
• Overexpression of Rnq1p sequesters N-terminal wild-type huntingtin fragment.
• Even here, effect of the polyglutamine-rich protein on cellular phenotype is obvious.

Aggregation of the N-terminal human mutant huntingtin and the consequent toxicity in the yeast model of Huntington's disease (HD) requires the presence of Rnq1 protein (Rnq1p) in its prion conformation [RNQ1+]. The understanding of interaction of wild-type huntingtin (wt-Htt) with the amyloidogenic prion has some gaps. In this work, we show that N-terminal fragment of wt-Htt (N-wt-Htt) ameliorated the toxic effect of [RNQ1+] depending on expression levels of both proteins. When the expression of N-wt-Htt was high, it increased the expression and delayed the aggregation of [RNQ1+]. As the expression of N-wt-Htt was reduced, it formed high molecular weight aggregates along with the prion. Even when sequestered by [RNQ1+], the beneficial effect of N-wt-Htt on expression of Rnq1p and on cell survival was evident. Huntingtin protein ameliorated toxicity due to the prion protein [RNQ1+] in yeast cells in a dose-dependent manner, resulting in increase in cell survival, hinting at its probable role as a component of the proteostasis network of the cell. Taking into account the earlier reports of the beneficial effect of expression of N-wt-Htt on the aggregation of mutant huntingtin, the function of wild-type huntingtin as an inhibitor of protein aggregation in the cell needs to be explored.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 590, 15 January 2016, Pages 82–89
نویسندگان
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