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Regulation of hypoxia-inducible factor-1α by NF-κB

HIF (hypoxia-inducible factor) is the main transcription factor activated by low oxygen tensions. HIF-1α (and other α subunits) is tightly controlled mostly at the protein level, through the concerted action of a class of enzymes called PHDs (prolyl hydroxylases) 1, 2 and 3. Most of the knowledge of...

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Autores principales: van Uden, Patrick, Kenneth, Niall S., Rocha, Sonia
Formato: Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474706/
https://www.ncbi.nlm.nih.gov/pubmed/18393939
http://dx.doi.org/10.1042/BJ20080476
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author van Uden, Patrick
Kenneth, Niall S.
Rocha, Sonia
author_facet van Uden, Patrick
Kenneth, Niall S.
Rocha, Sonia
author_sort van Uden, Patrick
collection PubMed
description HIF (hypoxia-inducible factor) is the main transcription factor activated by low oxygen tensions. HIF-1α (and other α subunits) is tightly controlled mostly at the protein level, through the concerted action of a class of enzymes called PHDs (prolyl hydroxylases) 1, 2 and 3. Most of the knowledge of HIF derives from studies following hypoxic stress; however, HIF-1α stabilization is also found in non-hypoxic conditions through an unknown mechanism. In the present study, we demonstrate that NF-κB (nuclear factor κB) is a direct modulator of HIF-1α expression. The HIF-1α promoter is responsive to selective NF-κB subunits. siRNA (small interfering RNA) studies for individual NF-κB members revealed differential effects on HIF-1α mRNA levels, indicating that NF-κB can regulate basal HIF-1α expression. Finally, when endogenous NF-κB is induced by TNFα (tumour necrosis factor α) treatment, HIF-1α levels also change in an NF-κB-dependent manner. In conclusion, we find that NF-κB can regulate basal TNFα and, in certain circumstances, the hypoxia-induced HIF-1α.
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spelling pubmed-24747062008-10-07 Regulation of hypoxia-inducible factor-1α by NF-κB van Uden, Patrick Kenneth, Niall S. Rocha, Sonia Biochem J Research Article HIF (hypoxia-inducible factor) is the main transcription factor activated by low oxygen tensions. HIF-1α (and other α subunits) is tightly controlled mostly at the protein level, through the concerted action of a class of enzymes called PHDs (prolyl hydroxylases) 1, 2 and 3. Most of the knowledge of HIF derives from studies following hypoxic stress; however, HIF-1α stabilization is also found in non-hypoxic conditions through an unknown mechanism. In the present study, we demonstrate that NF-κB (nuclear factor κB) is a direct modulator of HIF-1α expression. The HIF-1α promoter is responsive to selective NF-κB subunits. siRNA (small interfering RNA) studies for individual NF-κB members revealed differential effects on HIF-1α mRNA levels, indicating that NF-κB can regulate basal HIF-1α expression. Finally, when endogenous NF-κB is induced by TNFα (tumour necrosis factor α) treatment, HIF-1α levels also change in an NF-κB-dependent manner. In conclusion, we find that NF-κB can regulate basal TNFα and, in certain circumstances, the hypoxia-induced HIF-1α. Portland Press Ltd. 2008-05-28 2008-06-15 /pmc/articles/PMC2474706/ /pubmed/18393939 http://dx.doi.org/10.1042/BJ20080476 Text en © 2008 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited http://creativecommons.org/licenses/by-nc/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
van Uden, Patrick
Kenneth, Niall S.
Rocha, Sonia
Regulation of hypoxia-inducible factor-1α by NF-κB
title Regulation of hypoxia-inducible factor-1α by NF-κB
title_full Regulation of hypoxia-inducible factor-1α by NF-κB
title_fullStr Regulation of hypoxia-inducible factor-1α by NF-κB
title_full_unstemmed Regulation of hypoxia-inducible factor-1α by NF-κB
title_short Regulation of hypoxia-inducible factor-1α by NF-κB
title_sort regulation of hypoxia-inducible factor-1α by nf-κb
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474706/
https://www.ncbi.nlm.nih.gov/pubmed/18393939
http://dx.doi.org/10.1042/BJ20080476
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