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: In order to study the regulation of complex formation of endogenous HIF-1 in intact cells, we applied the in situ proximity ligation assay (PLA). Using this method, the HIF-1α/ARNT interaction was monitored in HeLa cells that were incubated under normoxic or hypoxic conditions. Following treatment with both anti-HIF-1α and anti-ARNT primary antibodies and analysis by in situ PLA, a very weak signal could be detected in cells incubated under normoxia while, in contrast, the signal was drastically amplified in cells grown under hypoxic conditions (Fig. 1a, panels i and ii and chart). The detected signals were specific for the HIF-1α/ARNT complex as no signal was obtained when one or both of the primary antibodies were omitted (Fig. 1a, panels iii–viii). We, therefore, concluded that in situ PLA could be used for specific detection of HIF-1α/ARNT heterodimerization in intact cells.
Affiliation: Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Larissa, Greece.