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Cells 2018, 7(8), 102;

TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway

Center for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD15EH, UK
Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool L697ZB, UK
Author to whom correspondence should be addressed.
Received: 29 June 2018 / Revised: 6 August 2018 / Accepted: 7 August 2018 / Published: 8 August 2018
(This article belongs to the Special Issue Gene Regulation by HIFs during Hypoxia)
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Non-canonical NF-κB signalling plays important roles in the development and function of the immune system but it also is deregulated in a number of inflammatory diseases. Although, NF-κB and HIF crosstalk has been documented, this has only been described following canonical NF-κB stimulation, involving RelA/p50 and the HIF-1 dimer. Here, we report that the non-canonical inducer TNFSF14/LIGHT leads to HIF induction and activation in cancer cells. We demonstrate that only HIF-2α is induced at the transcriptional level following non-canonical NF-κB activation, via a mechanism that is dependent on the p52 subunit. Furthermore, we demonstrate that p52 can bind to the HIF-2α promoter in cells. These results indicate that non-canonical NF-κB can lead to HIF signalling implicating HIF-2α as one of the downstream effectors of this pathway in cells. View Full-Text
Keywords: HIF; NF-κB; EPAS1; LIGHT; TNFSF14; p52; NIK; ChIP HIF; NF-κB; EPAS1; LIGHT; TNFSF14; p52; NIK; ChIP

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D’Ignazio, L.; Batie, M.; Rocha, S. TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway. Cells 2018, 7, 102.

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