کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1935024 1050656 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sumoylation of amyloid precursor protein negatively regulates Aβ aggregate levels
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Sumoylation of amyloid precursor protein negatively regulates Aβ aggregate levels
چکیده انگلیسی

The proteolytic processing of amyloid precursor protein (APP) to produce Aβ peptides is thought to play an important role in the mechanism of Alzheimer’s disease. Here, we show that lysines 587 and 595 of APP, which are immediately adjacent to the site of β-secretase cleavage, are covalently modified by SUMO proteins in vivo. Sumoylation of these lysine residues is associated with decreased levels of Aβ aggregates. Further, overexpression of the SUMO E2 enzyme ubc9 along with SUMO-1 results in decreased levels of Aβ aggregates in cells transfected with the familial Alzheimer’s disease-associated V642F mutant APP, indicating the potential of up-regulating activity of the cellular sumoylation machinery as an approach against Alzheimer’s disease. The results also provide the first demonstration that the SUMO E2 enzyme (ubc9) is present within the endoplasmic reticulum, indicating how APP, and perhaps other proteins that enter this compartment, can be sumoylated.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 374, Issue 4, 3 October 2008, Pages 673–678
نویسندگان
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