کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10756354 1050382 2014 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Prostaglandin receptor EP1-mediated differential degradation of cyclooxygenases involves a specific lysine residue
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Prostaglandin receptor EP1-mediated differential degradation of cyclooxygenases involves a specific lysine residue
چکیده انگلیسی
The cyclooxygenase (COX) enzyme isoforms COX-1 and COX-2 catalyze the main step in the generation of prostanoids that mediate major physiological functions. Whereas COX-1 is a ubiquitously expressed stable protein, COX-2 is transiently upregulated in many pathologies and is often associated with a poor prognostic outcome. We have recently shown that an interaction of COX-2 with the prostaglandin EP1 receptor accelerates its degradation via a mechanism that augments its level of ubiquitination. Here we show that the sensitivity of both COX-1 and COX-2 to EP1 is altered upon modification of one lysine residue. A point mutation of lysine to-arginine in position 432 of COX-2 (K432R) yields an enzyme with decreased sensitivity to EP1-mediated degradation. In contrast, insertion of a putative ubiquitination site into the corresponding position of COX-1 (H446K′) yields an enzyme with higher levels of ubiquitination and reduced expression. Furthermore, compared to wild type COX-1, H446K′ is significantly more sensitive to downregulation by EP1. Together these data suggest that distinctive ubiquitination of COX-1 and COX-2 may be responsible for their different sensitivity to EP1-mediated degradation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 443, Issue 2, 10 January 2014, Pages 738-742
نویسندگان
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