کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5916452 | 1163742 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activated PKR inhibits pancreatic β-cell proliferation through sumoylation-dependent stabilization of P53
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
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چکیده انگلیسی
Double-stranded RNA-dependent protein kinase (PKR) is intimately involved in type 2 diabetes due to its role in insulin resistance in peripheral tissues and anti-proliferative effect on pancreatic β-cells. Activated PKR was found to inhibit β-cell proliferation, partially through accumulation of P53. However the molecular mechanisms underlying PKR-dependent upregulation of P53 remain unknown. The results of the present study showed that PKR can be specifically activated in PKR overexpressing β-cells by a low dosage of the previously synthesized compound 1H-benzimidazole1-ethanol,2,3-dihydro-2-imino-a-(phenoxymethyl)-3-(phenylmethyl)-,monohydrochloride (BEPP), and this led to upregulation of P53 through sumoylation-dependent stability. Activated PKR was found to interact with sumo-conjugating enzyme Ubc9, and P53 sumoylation relies on a PKR-Ubc9 protein-protein interaction. Additionally, a ceramide signal was needed for PKR activation to be triggered by glucolipotoxicity and TNFα stimulation, and stabilization of P53 required endogenous ceramide accumulation. Glucolipotoxicity and pro-inflammatory cytokines therefore promote the sumoylation-dependent stability of P53 via the ceramide/PKR/Ubc9 signalling pathway that is involved in pancreatic β-cell proliferation inhibition in the development of type 2 diabetes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 68, Issue 2, Part A, December 2015, Pages 341-349
Journal: Molecular Immunology - Volume 68, Issue 2, Part A, December 2015, Pages 341-349
نویسندگان
Ying Song, XiaoMeng Wan, LiLi Gao, Yi Pan, WeiPing Xie, Hong Wang, Jun Guo,