کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8452152 | 1547700 | 2017 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
G protein-coupled receptor kinase 4-induced cellular senescence and its senescence-associated gene expression profiling
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کلمات کلیدی
CDKCCK-8FACSGPCRSA-β-galGRKCKIG protein-coupled receptor kinases - G پروتئین گیرنده kinasesfluorescence-activated cell sorting - دسته بندی سلول های فعال فلورسنسcell counting kit-8 - شمارش سلول کیت 8gene expression profiling - مشخصات ژن بیانcyclin-dependent kinase inhibitor - مهار کننده کیناز وابسته به سیکلینsenescence-associated-β-galactosidase - پیری زودرس، بتا گالاکتوزیدازCellular senescence - پیری سلولیcyclin-dependent kinase - کییناز وابسته به سیکلینG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Senescent cells have lost their capacity for proliferation and manifest as irreversibly in cell cycle arrest. Many membrane receptors, including G protein-coupled receptors (GPCRs), initiate a variety of intracellular signaling cascades modulating cell division and potentially play roles in triggering cellular senescence response. GPCR kinases (GRKs) belong to a family of serine/threonine kinases. Although their role in homologous desensitization of activated GPCRs is well established, the involvement of the kinases in cell proliferation is still largely unknown. In this study, we isolated GRK4-GFP expressing HEK293 cells by fluorescence-activated cell sorting (FACS) and found that the ectopic expression of GRK4 halted cell proliferation. Cells expressing GRK4 (GRK4(+)) demonstrated cell cycle G1/G0 phase arrest, accompanied with significant increase of senescence-associated-β-galactosidase (SA-β-Gal) activity. Expression profiling analysis of 78 senescence-related genes by qRT-PCR showed a total of 17 genes significantly changed in GRK4(+) cells (⥠2 fold, p < 0.05). Among these, 9 genes - AKT1, p16INK4, p27KIP1, p19INK4, IGFBP3, MAPK14, PLAU, THBS1, TP73 - were up-regulated, while 8 genes, Cyclin A2, Cyclin D1, CDK2, CDK6, ETS1, NBN, RB1, SIRT1, were down-regulated. The increase in cyclin-dependent kinase inhibitors (p16, p27) and p38 MAPK proteins (MAPK14) was validated by immunoblotting. Neither p53 nor p21Waf1/Cip1 protein was detectable, suggesting no p53 activation in the HEK293 cells. These results unveil a novel function of GRK4 on triggering a p53-independent cellular senescence, which involves an intricate signaling network.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 360, Issue 2, 15 November 2017, Pages 273-280
Journal: Experimental Cell Research - Volume 360, Issue 2, 15 November 2017, Pages 273-280
نویسندگان
Pingping Xiao, Xishi Huang, Lanzhen Huang, Jing Yang, Ang Li, Ke Shen, Philip B. Wedegaertner, Xiaoshan Jiang,