dc.creator | Pangou E., Befani C., Mylonis I., Samiotaki M., Panayotou G., Simos G., Liakos P. | en |
dc.date.accessioned | 2023-01-31T09:41:41Z | |
dc.date.available | 2023-01-31T09:41:41Z | |
dc.date.issued | 2016 | |
dc.identifier | 10.1242/jcs.191395 | |
dc.identifier.issn | 00219533 | |
dc.identifier.uri | http://hdl.handle.net/11615/77487 | |
dc.description.abstract | Hypoxia inducible factor 2 (HIF-2) is a transcriptional activator implicated in the cellular response to hypoxia. Regulation of its inducible subunit, HIF-2α (also known as EPAS1), involves posttranslational modifications. Here, we demonstrate that casein kinase 1d (CK1δ; also known as CSNK1D) phosphorylates HIF-2α at Ser383 and Thr528 in vitro.We found that disruption of these phosphorylation sites, and silencing or chemical inhibition of CK1δ, reduced the expression of HIF-2 target genes and the secretion of erythropoietin (EPO) in two hepatic cancer cell lines, Huh7 and HepG2, without affecting the levels of HIF-2α protein expression. Furthermore, when CK1δ-dependent phosphorylation of HIF-2α was inhibited, we observed substantial cytoplasmic mislocalization of HIF-2α, which was reversed upon the addition of the nuclear protein export inhibitor leptomycin B. Taken together, these data suggest that CK1δ enhances EPO secretion from liver cancer cells under hypoxia by modifying HIF-2α and promoting its nuclear accumulation. This modification represents a new mechanism of HIF-2 regulation that might allow HIF isoforms to undertake differing functions. © 2016. | en |
dc.language.iso | en | en |
dc.source | Journal of Cell Science | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84995947052&doi=10.1242%2fjcs.191395&partnerID=40&md5=836950a3b2ead66006ee94057a6a7dd5 | |
dc.subject | casein kinase Idelta | en |
dc.subject | erythropoietin | en |
dc.subject | hypoxia inducible factor 2alpha | en |
dc.subject | leptomycin B | en |
dc.subject | serine | en |
dc.subject | threonine | en |
dc.subject | upstream stimulatory factor 2 | en |
dc.subject | basic helix loop helix transcription factor | en |
dc.subject | casein kinase Idelta | en |
dc.subject | cell receptor | en |
dc.subject | endothelial PAS domain-containing protein 1 | en |
dc.subject | erythropoietin | en |
dc.subject | exportin 1 protein | en |
dc.subject | karyopherin | en |
dc.subject | protein binding | en |
dc.subject | upstream stimulatory factor | en |
dc.subject | USF2 protein, human | en |
dc.subject | Article | en |
dc.subject | cancer cell | en |
dc.subject | cell hypoxia | en |
dc.subject | controlled study | en |
dc.subject | cytokine release | en |
dc.subject | cytoplasm | en |
dc.subject | gene expression | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | in vitro study | en |
dc.subject | liver cancer | en |
dc.subject | liver cancer cell line | en |
dc.subject | nuclear export signal | en |
dc.subject | priority journal | en |
dc.subject | protein expression | en |
dc.subject | protein function | en |
dc.subject | protein phosphorylation | en |
dc.subject | protein stability | en |
dc.subject | regulatory mechanism | en |
dc.subject | transcription initiation | en |
dc.subject | amino acid sequence | en |
dc.subject | cell hypoxia | en |
dc.subject | cell nucleus | en |
dc.subject | chemistry | en |
dc.subject | gene silencing | en |
dc.subject | genetic transcription | en |
dc.subject | genetics | en |
dc.subject | HeLa cell line | en |
dc.subject | Hep-G2 cell line | en |
dc.subject | liver tumor | en |
dc.subject | metabolism | en |
dc.subject | mutation | en |
dc.subject | nucleocytoplasmic transport | en |
dc.subject | pathology | en |
dc.subject | phosphorylation | en |
dc.subject | secretion (process) | en |
dc.subject | Active Transport, Cell Nucleus | en |
dc.subject | Amino Acid Sequence | en |
dc.subject | Basic Helix-Loop-Helix Transcription Factors | en |
dc.subject | Casein Kinase Idelta | en |
dc.subject | Cell Hypoxia | en |
dc.subject | Cell Nucleus | en |
dc.subject | Erythropoietin | en |
dc.subject | Gene Silencing | en |
dc.subject | HeLa Cells | en |
dc.subject | Hep G2 Cells | en |
dc.subject | Humans | en |
dc.subject | Karyopherins | en |
dc.subject | Liver Neoplasms | en |
dc.subject | Mutation | en |
dc.subject | Phosphorylation | en |
dc.subject | Protein Binding | en |
dc.subject | Protein Stability | en |
dc.subject | Receptors, Cytoplasmic and Nuclear | en |
dc.subject | Transcription, Genetic | en |
dc.subject | Upstream Stimulatory Factors | en |
dc.subject | Company of Biologists Ltd | en |
dc.title | HIF-2α phosphorylation by CK1δ promotes erythropoietin secretion in liver cancer cells under hypoxia | en |
dc.type | journalArticle | en |