کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2132535 1086699 2007 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PERK-dependent compartmentalization of ERAD and unfolded protein response machineries during ER stress
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
PERK-dependent compartmentalization of ERAD and unfolded protein response machineries during ER stress
چکیده انگلیسی
Accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the ER membrane kinases PERK and IRE1 leading to the unfolded protein response (UPR). We show here that UPR activation triggers PERK and IRE1 segregation from BiP and their sorting with misfolded proteins to the ER-derived quality control compartment (ERQC), a pericentriolar compartment that we had identified previously. PERK phosphorylates translation factor eIF2α, which then accumulates on the cytosolic side of the ERQC. Dominant negative PERK or eIF2α(S51A) mutants prevent the compartmentalization, whereas eIF2α(S51D) mutant, which mimics constitutive phosphorylation, promotes it. This suggests a feedback loop where eIF2α phosphorylation causes pericentriolar concentration at the ERQC, which in turn amplifies the UPR. ER-associated degradation (ERAD) is an UPR-dependent process; we also find that ERAD components (Sec61β, HRD1, p97/VCP, ubiquitin) are recruited to the ERQC, making it a likely site for retrotranslocation. In addition, we show that autophagy, suggested to play a role in elimination of aggregated proteins, is unrelated to protein accumulation in the ERQC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 313, Issue 16, 1 October 2007, Pages 3395-3407
نویسندگان
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