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Cobalt stimulates HIF-1-dependent but inhibits HIF-2-dependent gene expression in liver cancer cells
dc.creator | Befani, C. | en |
dc.creator | Mylonis, I. | en |
dc.creator | Gkotinakou, I. M. | en |
dc.creator | Georgoulias, P. | en |
dc.creator | Hu, C. J. | en |
dc.creator | Simos, G. | en |
dc.creator | Liakos, P. | en |
dc.date.accessioned | 2015-11-23T10:23:41Z | |
dc.date.available | 2015-11-23T10:23:41Z | |
dc.date.issued | 2013 | |
dc.identifier | 10.1016/j.biocel.2013.07.025 | |
dc.identifier.issn | 1357-2725 | |
dc.identifier.uri | http://hdl.handle.net/11615/26215 | |
dc.description.abstract | Hypoxia-inducible factors (HIFs) are transcriptional regulators that mediate the cellular response to low oxygen. Although HIF-1 is usually considered as the principal mediator of hypoxic adaptation, several tissues and different cell types express both HIF-1 and HIF-2 isoforms under hypoxia or when treated with hypoxia mimetic chemicals such as cobalt. However, the similarities or differences between HIFI and HIF-2, in terms of their tissue- and inducer-specific activation and function, are not adequately characterized. To address this issue, we investigated the effects of true hypoxia and hypoxia mimetics on HIF-1 and HIF-2 induction and specific gene transcriptional activity in two hepatic cancer cell lines, Huh7 and HepG2. Both hypoxia and cobalt caused rapid induction of both HIF-l alpha and HIF-2 alpha proteins. Hypoxia induced erythropoietin (EPO) expression and secretion in a HIF-2-dependent way. Surprisingly, however, EPO expression was not induced when cells were treated with cobalt. In agreement, both HIFI - and HIF-2-dependent promoters (of PGK and SOD2 genes, respectively) were activated by hypoxia while cobalt only activated the HIF-1-dependent PGK promoter. Unlike cobalt, other hypoxia mimetics such as DFO and DMOG activated both types of promoters. Furthermore, cobalt impaired the hypoxic stimulation of HIF-2, but not HIF-1, activity and cobalt-induced HIF-2a interacted poorly with USF-2, a HIF-2-specific co-activator. These data show that, despite similar induction of HIF-la and HIF-2a protein expression, HIF-1 and HIF-2 specific gene activating functions respond differently to different stimuli and suggest the operation of oxygen-independent and gene- or tissue-specific regulatory mechanisms involving additional transcription factors or co-activators. (C) 2013 Elsevier Ltd. All rights reserved. | en |
dc.source | International Journal of Biochemistry & Cell Biology | en |
dc.source.uri | <Go to ISI>://WOS:000327914800002 | |
dc.subject | HIF-2 alpha | en |
dc.subject | EPO | en |
dc.subject | SOD2 | en |
dc.subject | Hypoxia | en |
dc.subject | Cobalt | en |
dc.subject | USF2 | en |
dc.subject | HYPOXIA-INDUCIBLE FACTORS | en |
dc.subject | TARGET GENE | en |
dc.subject | HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA | en |
dc.subject | HIF-1-ALPHA | en |
dc.subject | HEPATOCELLULAR-CARCINOMA | en |
dc.subject | HIF-2-ALPHA EXPRESSION | en |
dc.subject | NUCLEAR | en |
dc.subject | ACCUMULATION | en |
dc.subject | FACTOR (HIF)-1-ALPHA | en |
dc.subject | PROLYL-HYDROXYLASES | en |
dc.subject | FACTOR 2-ALPHA | en |
dc.subject | FACTOR-I | en |
dc.subject | Biochemistry & Molecular Biology | en |
dc.subject | Cell Biology | en |
dc.title | Cobalt stimulates HIF-1-dependent but inhibits HIF-2-dependent gene expression in liver cancer cells | en |
dc.type | journalArticle | en |
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