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: To confirm the loss-of-function experiments using CK1δ inhibition in a positive way, we then examined lipid droplet formation in HeLa cells overexpressing catalytically active CK1δ or, as negative control, the catalytically inactive CK1δ K38M mutant (Supplementary Fig. 1a) . Under hypoxia, lipid droplet formation was decreased when the wild type form of CK1δ was overexpressed, whereas expression of its mutant inactive form K38M did not have any effect on lipid droplet formation (Fig. 6). We conclude that CK1δ limits neutral lipid synthesis under hypoxia, and this is most likely mediated by inhibition of heterodimerization and transcriptional activity of HIF-1.
Affiliation: Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Larissa, Greece.