Evolutionary conserved regulation of HIF-1β by NF-κB.
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 enzyme...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3029248?pdf=render |
| _version_ | 1818544413009248256 |
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| author | Patrick van Uden Niall S Kenneth Ryan Webster H Arno Müller Sharon Mudie Sonia Rocha |
| author_facet | Patrick van Uden Niall S Kenneth Ryan Webster H Arno Müller Sharon Mudie Sonia Rocha |
| author_sort | Patrick van Uden |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T22:48:11Z |
| format | Article |
| id | doaj.art-1c8bade540f340e6ba00a5cacc4b1071 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-11T22:48:11Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-1c8bade540f340e6ba00a5cacc4b10712022-12-22T00:47:33ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-01-0171e100128510.1371/journal.pgen.1001285Evolutionary conserved regulation of HIF-1β by NF-κB.Patrick van UdenNiall S KennethRyan WebsterH Arno MüllerSharon MudieSonia RochaHypoxia 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.http://europepmc.org/articles/PMC3029248?pdf=render |
| spellingShingle | Patrick van Uden Niall S Kenneth Ryan Webster H Arno Müller Sharon Mudie Sonia Rocha Evolutionary conserved regulation of HIF-1β by NF-κB. PLoS Genetics |
| title | Evolutionary conserved regulation of HIF-1β by NF-κB. |
| title_full | Evolutionary conserved regulation of HIF-1β by NF-κB. |
| title_fullStr | Evolutionary conserved regulation of HIF-1β by NF-κB. |
| title_full_unstemmed | Evolutionary conserved regulation of HIF-1β by NF-κB. |
| title_short | Evolutionary conserved regulation of HIF-1β by NF-κB. |
| title_sort | evolutionary conserved regulation of hif 1β by nf κb |
| url | http://europepmc.org/articles/PMC3029248?pdf=render |
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