dc.creator | Gkotinakou I.M., Befani C., Samiotaki M., Panayotou G., Liakos P. | en |
dc.date.accessioned | 2023-01-31T07:43:05Z | |
dc.date.available | 2023-01-31T07:43:05Z | |
dc.date.issued | 2021 | |
dc.identifier | 10.1016/j.bbrc.2021.03.176 | |
dc.identifier.issn | 0006291X | |
dc.identifier.uri | http://hdl.handle.net/11615/72512 | |
dc.description.abstract | Hypoxia-inducible factor 2 (HIF-2), is essential for cellular response to hypoxia and holds an important role in erythropoiesis, angiogenesis, tissue invasion and metastasis, thus, constituting an important therapeutic target. Maximal HIF-2 transcriptional activation requires HIF-2α phosphorylation by ERK1/2 that impairs its CRM1-mediated nuclear export. Herein, we reveal a novel interaction of HIF-2α with Reptin52, a multifunctional protein involved in cellular functions orchestrated both in the nucleus and the cytoplasm. HIF-2α and Reptin52 interact both in nuclear and cytoplasmic fractions, however, ERK1/2 pathway inactivation seems to favour their association in the cytoplasm. Notably, we demonstrate that Reptin52 reduces HIF-2 transcriptional activity, which results in decreased EPO secretion under hypoxia, by impairing HIF-2α stability via a non-canonical PHD-VHL-proteasome independent mechanism. This interaction represents a novel HIF-2 fine tuning mechanism that allows for distinct HIF1/2 isoforms regulation. © 2021 Elsevier Inc. | en |
dc.language.iso | en | en |
dc.source | Biochemical and Biophysical Research Communications | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85104063631&doi=10.1016%2fj.bbrc.2021.03.176&partnerID=40&md5=52c7a8544abf860eed110d641dede0ba | |
dc.subject | cell protein | en |
dc.subject | erythropoietin | en |
dc.subject | hypoxia inducible factor 2alpha | en |
dc.subject | isoprotein | en |
dc.subject | mitogen activated protein kinase 1 | en |
dc.subject | mitogen activated protein kinase 3 | en |
dc.subject | reptin52 | en |
dc.subject | unclassified drug | en |
dc.subject | AAA protein | en |
dc.subject | basic helix loop helix transcription factor | en |
dc.subject | carrier protein | en |
dc.subject | DNA helicase | en |
dc.subject | endothelial PAS domain-containing protein 1 | en |
dc.subject | EPO protein, human | en |
dc.subject | erythropoietin | en |
dc.subject | MAPK1 protein, human | en |
dc.subject | MAPK3 protein, human | en |
dc.subject | mitogen activated protein kinase 1 | en |
dc.subject | mitogen activated protein kinase 3 | en |
dc.subject | proteasome | en |
dc.subject | RUVBL2 protein, human | en |
dc.subject | small interfering RNA | en |
dc.subject | Article | en |
dc.subject | cell culture | en |
dc.subject | cell function | en |
dc.subject | controlled study | en |
dc.subject | cytoplasm | en |
dc.subject | down regulation | en |
dc.subject | enzyme inactivation | en |
dc.subject | HeLa cell line | en |
dc.subject | Huh-7 cell line | en |
dc.subject | immunoblotting | en |
dc.subject | immunoprecipitation | en |
dc.subject | in vitro study | en |
dc.subject | liquid chromatography-mass spectrometry | en |
dc.subject | luciferase assay | en |
dc.subject | polyacrylamide gel electrophoresis | en |
dc.subject | protein expression | en |
dc.subject | protein function | en |
dc.subject | protein protein interaction | en |
dc.subject | protein purification | en |
dc.subject | protein secretion | en |
dc.subject | protein stability | en |
dc.subject | quantitative analysis | en |
dc.subject | reverse transcription polymerase chain reaction | en |
dc.subject | RNA extraction | en |
dc.subject | signal transduction | en |
dc.subject | cell hypoxia | en |
dc.subject | cell nucleus | en |
dc.subject | erythropoiesis | en |
dc.subject | gene expression regulation | en |
dc.subject | genetics | en |
dc.subject | human | en |
dc.subject | liquid chromatography | en |
dc.subject | MAPK signaling | en |
dc.subject | metabolism | en |
dc.subject | phosphorylation | en |
dc.subject | real time polymerase chain reaction | en |
dc.subject | tandem mass spectrometry | en |
dc.subject | tumor cell line | en |
dc.subject | ATPases Associated with Diverse Cellular Activities | en |
dc.subject | Basic Helix-Loop-Helix Transcription Factors | en |
dc.subject | Carrier Proteins | en |
dc.subject | Cell Hypoxia | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Cell Nucleus | en |
dc.subject | Chromatography, Liquid | en |
dc.subject | Cytoplasm | en |
dc.subject | DNA Helicases | en |
dc.subject | Erythropoiesis | en |
dc.subject | Erythropoietin | en |
dc.subject | Gene Expression Regulation | en |
dc.subject | Humans | en |
dc.subject | MAP Kinase Signaling System | en |
dc.subject | Mitogen-Activated Protein Kinase 1 | en |
dc.subject | Mitogen-Activated Protein Kinase 3 | en |
dc.subject | Phosphorylation | en |
dc.subject | Proteasome Endopeptidase Complex | en |
dc.subject | Protein Stability | en |
dc.subject | Real-Time Polymerase Chain Reaction | en |
dc.subject | RNA, Small Interfering | en |
dc.subject | Tandem Mass Spectrometry | en |
dc.subject | Elsevier B.V. | en |
dc.title | Novel HIF-2α interaction with Reptin52 impairs HIF-2 transcriptional activity and EPO secretion | en |
dc.type | journalArticle | en |