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Cells 2018, 7(8), 102; https://doi.org/10.3390/cells7080102

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

1
Center for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD15EH, UK
2
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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Abstract

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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