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CK1 delta restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1 alpha/ARNT complex formation
dc.creator | Kourti, M. | en |
dc.creator | Ikonomou, G. | en |
dc.creator | Giakoumakis, N. N. | en |
dc.creator | Rapsomaniki, M. A. | en |
dc.creator | Landegren, U. | en |
dc.creator | Siniossoglou, S. | en |
dc.creator | Lygerou, Z. | en |
dc.creator | Simos, G. | en |
dc.creator | Mylonis, I. | en |
dc.date.accessioned | 2015-11-23T10:36:27Z | |
dc.date.available | 2015-11-23T10:36:27Z | |
dc.date.issued | 2015 | |
dc.identifier | 10.1016/j.cellsig.2015.02.017 | |
dc.identifier.issn | 0898-6568 | |
dc.identifier.uri | http://hdl.handle.net/11615/29879 | |
dc.description.abstract | Proliferation of cells under hypoxia is facilitated by metabolic adaptation, mediated by the transcriptional activator Hypoxia Inducible Factor-1 (HIF-1). HIF-1 alpha, the inducible subunit of HIF-1 is regulated by oxygen as well as by oxygen-independent mechanisms involving phosphorylation. We have previously shown that CK1 delta phosphorylates HIP-la 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 HIP-1 alpha interactions within the cell nucleus using the in situ proximity ligation assay (PIA) and fluorescence recovery after photobleaching (FRAP). Both methods show that CK1 delta-dependent modification of HIF-1 alpha 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 CK1 delta increases lipid droplet formation and proliferation of both cancer and normal cells specifically under hypoxia and in an HIF-1 alpha- and lipin-1-dependent manner. These data reveal a novel role for CK1 delta in regulating lipid metabolism and, through it, cell adaptation to low oxygen conditions. (C) 2015 The Authors. Published by Elsevier Inc. | en |
dc.source | Cellular Signalling | en |
dc.source.uri | <Go to ISI>://WOS:000353096700010 | |
dc.subject | Hypoxia | en |
dc.subject | Lipid metabolism | en |
dc.subject | CK1 delta | en |
dc.subject | HIF-1 | en |
dc.subject | Lipin1 | en |
dc.subject | Lipid droplets | en |
dc.subject | TRANSCRIPTIONAL ACTIVITY | en |
dc.subject | DIRECT PHOSPHORYLATION | en |
dc.subject | GLUTAMINE-METABOLISM | en |
dc.subject | CANCER PROGRESSION | en |
dc.subject | INDUCIBLE FACTORS | en |
dc.subject | WNT/BETA-CATENIN | en |
dc.subject | TUMOR-GROWTH | en |
dc.subject | IN-VITRO | en |
dc.subject | KINASE | en |
dc.subject | BINDING | en |
dc.subject | Cell Biology | en |
dc.title | CK1 delta restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1 alpha/ARNT complex formation | en |
dc.type | journalArticle | en |
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