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

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-&a...

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Main Authors: Laura D’Ignazio, Michael Batie, Sonia Rocha
Format: Article
Language:English
Published: MDPI AG 2018-08-01
Series:Cells
Subjects:
Online Access:http://www.mdpi.com/2073-4409/7/8/102
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author Laura D’Ignazio
Michael Batie
Sonia Rocha
author_facet Laura D’Ignazio
Michael Batie
Sonia Rocha
author_sort Laura D’Ignazio
collection DOAJ
description 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.
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spelling doaj.art-0eb130c569584fa184aacaab4455541d2023-09-02T15:23:37ZengMDPI AGCells2073-44092018-08-017810210.3390/cells7080102cells7080102TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF PathwayLaura D’Ignazio0Michael Batie1Sonia Rocha2Center for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD15EH, UKDepartment of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool L697ZB, UKCenter for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD15EH, UKNon-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.http://www.mdpi.com/2073-4409/7/8/102HIFNF-κBEPAS1LIGHTTNFSF14p52NIKChIP
spellingShingle Laura D’Ignazio
Michael Batie
Sonia Rocha
TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway
Cells
HIF
NF-κB
EPAS1
LIGHT
TNFSF14
p52
NIK
ChIP
title TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway
title_full TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway
title_fullStr TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway
title_full_unstemmed TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway
title_short TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway
title_sort tnfsf14 light a non canonical nf κb stimulus induces the hif pathway
topic HIF
NF-κB
EPAS1
LIGHT
TNFSF14
p52
NIK
ChIP
url http://www.mdpi.com/2073-4409/7/8/102
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