CK1δ restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1α/ARNT complex formation.
Bottom Line: We have previously shown that CK1δ phosphorylates HIF-1α in its N-terminus and reduces its affinity for its heterodimerization partner ARNT.This is confirmed by analyzing expression of lipin-1, a direct target of HIF-1 that mediates hypoxic neutral lipid accumulation.These data reveal a novel role for CK1δ in regulating lipid metabolism and, through it, cell adaptation to low oxygen conditions.
Affiliation: Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Larissa, Greece.Show MeSH
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Mentions: Having established the suitability of in situ PLA for generating quantifiable data in a cell-based system, we investigated the effect of CK1δ on the formation of HIF-1 complexes. HeLa cells were co-transfected with a CK1δ overexpressing plasmid (pcDNA3.1-CK1δ) or the corresponding empty vector (pcDNA3.1) and a GFP expressing plasmid (pEGFP; to detect transfected cells) and incubated under hypoxic conditions (Supplementary Fig. 1a). Visualization and quantification of the PLA signals show a significant decrease in the number of HIF-1α/ARNT complexes specifically in cells that overexpress CK1δ compared to control cells that are transfected with the empty vector (Fig. 2a) Therefore, CK1δ does indeed inhibit HIF-1 heterodimerization in intact cells in accordance with our previous in vitro experiments .
Affiliation: Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Larissa, Greece.