کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815053 | 1058444 | 2015 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
CK1δ restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1α/ARNT complex formation
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کلمات کلیدی
PLAHIF-1FRAPCK1HIFARNTCK1δProximity ligation assay - آزمون لمس نزدیکیaryl hydrocarbon receptor nuclear translocator - اتمسفر هسته ای گیرنده آرویل کربنHypoxia-inducible factor - فاکتور القاء کننده هیپوکسیfluorescence recovery after photobleaching - فلوئورسانس پس از فوتوبلاسیکLipid droplets - قطرات لیپیدLipid metabolism - متابولیسم لیپیدHypoxia - هیپوکسیcasein kinase 1 - کازئین کیناز 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Proliferation of cells under hypoxia is facilitated by metabolic adaptation, mediated by the transcriptional activator Hypoxia Inducible Factor-1 (HIF-1). HIF-1α, the inducible subunit of HIF-1 is regulated by oxygen as well as by oxygen-independent mechanisms involving phosphorylation. We have previously shown that CK1δ phosphorylates HIF-1α in its N-terminus and reduces its affinity for its heterodimerization partner ARNT. To investigate the importance of this mechanism for cell proliferation under hypoxia, we visually monitored HIF-1α interactions within the cell nucleus using the in situ proximity ligation assay (PLA) and fluorescence recovery after photobleaching (FRAP). Both methods show that CK1δ-dependent modification of HIF-1α impairs the formation of a chromatin binding HIF-1 complex. This is confirmed by analyzing expression of lipin-1, a direct target of HIF-1 that mediates hypoxic neutral lipid accumulation. Inhibition of CK1δ increases lipid droplet formation and proliferation of both cancer and normal cells specifically under hypoxia and in an HIF-1α- and lipin-1-dependent manner. These data reveal a novel role for CK1δ in regulating lipid metabolism and, through it, cell adaptation to low oxygen conditions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 6, June 2015, Pages 1129-1140
Journal: Cellular Signalling - Volume 27, Issue 6, June 2015, Pages 1129-1140
نویسندگان
Maria Kourti, Georgia Ikonomou, Nikolaos-Nikiforos Giakoumakis, Maria Anna Rapsomaniki, Ulf Landegren, Symeon Siniossoglou, Zoi Lygerou, George Simos, Ilias Mylonis,