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Reference Report
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| Citation | van Uden, P., Kenneth, N.S., Webster, R., Müller, H.A., Mudie, S., Rocha, S. (2011). Evolutionary Conserved Regulation of HIF-1β by NF-κB. PLoS Genet. 7(1): e1001285. (Export to RIS) | ||
| FlyBase ID | FBrf0212948 | ||
| Publication Type | Research paper | ||
| PubMed ID | 21298084 | ||
| PubMed Abstract | Hypoxia Inducible Factor-1 (HIF-1) is essential for mammalian development and is the principal transcription factor activated by low oxygen tensions. HIF-α subunit quantities and their associated activity are regulated in a post-translational manner, through the concerted action of a class of enzymes called Prolyl Hydroxylases (PHDs) and Factor Inhibiting HIF (FIH) respectively. However, alternative modes of HIF-α regulation such as translation or transcription are under-investigated, and their importance has not been firmly established. Here, we demonstrate that NF-κB regulates the HIF pathway in a significant and evolutionary conserved manner. We demonstrate that NF-κB directly regulates HIF-1β mRNA and protein. In addition, we found that NF-κB-mediated changes in HIF-1β result in modulation of HIF-2α protein. HIF-1β overexpression can rescue HIF-2α protein levels following NF-κB depletion. Significantly, NF-κB regulates HIF-1β (tango) and HIF-α (sima) levels and activity (Hph/fatiga, ImpL3/ldha) in Drosophila, both in normoxia and hypoxia, indicating an evolutionary conserved mode of regulation. These results reveal a novel mechanism of HIF regulation, with impact in the development of novel therapeutic strategies for HIF-related pathologies including ageing, ischemia, and cancer. | ||
| DOI | 10.1371/journal.pgen.1001285 | ||
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| Language of Publication | English | ||
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| Publication Type | Journal | ||
| Abbreviation | PLoS Genet. | ||
| Title | PLoS Genetics | ||
| Publication Year | 2005- | ||
| ISBN/ISSN | 1553-7404 1553-7390 | ||
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Data from Reference
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| Aberrations (1)
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| Alleles (7)
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| Constructs (2)
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| Genes (10)
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