کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10956709 | 1099416 | 2009 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Phosphorylation of huntingtin reduces the accumulation of its nuclear fragments
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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![عکس صفحه اول مقاله: Phosphorylation of huntingtin reduces the accumulation of its nuclear fragments Phosphorylation of huntingtin reduces the accumulation of its nuclear fragments](/preview/png/10956709.png)
چکیده انگلیسی
Huntingtin is phosphorylated on serine-421 (S421) by the pro-survival signaling protein kinases Akt and SGK. Phosphorylation of huntingtin at S421 is variable in different regions of the brain with the lowest levels observed in the striatum, which is further reduced by the mutation for Huntington disease (HD). Cleavage of huntingtin by caspase-6Â at amino acid 586 is a crucial event in the pathogenesis of HD. Nuclear localization of huntingtin is also an important marker of HD and preventing or delaying its nuclear accumulation is protective in disease models. Phosphorylation influences proteolysis and clearance of many protein substrates. We therefore sought to investigate the influence of huntingtin phosphorylation at S421 on the accumulation of huntingtin-caspase-6 fragments because these fragments are generated in the nucleus and are crucial for the disease phenotype. Using phospho-huntingtin mutants and a cleavage site-specific neo-epitope huntingtin antibody, we demonstrate that phosphorylation at S421 reduces the nuclear accumulation of huntingtin-caspase-6 fragments by reducing huntingtin cleavage by caspase-6, the levels of full-length huntingtin, and its nuclear localization.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 40, Issue 2, February 2009, Pages 121-127
Journal: Molecular and Cellular Neuroscience - Volume 40, Issue 2, February 2009, Pages 121-127
نویسندگان
Simon C. Warby, Crystal N. Doty, Rona K. Graham, Jonathan Shively, Roshni R. Singaraja, Michael R. Hayden,