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...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2018-08-01
|
Series: | Cells |
Subjects: | |
Online Access: | http://www.mdpi.com/2073-4409/7/8/102 |
_version_ | 1797719404237029376 |
---|---|
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. |
first_indexed | 2024-03-12T09:04:24Z |
format | Article |
id | doaj.art-0eb130c569584fa184aacaab4455541d |
institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-12T09:04:24Z |
publishDate | 2018-08-01 |
publisher | MDPI AG |
record_format | Article |
series | Cells |
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 |
work_keys_str_mv | AT lauradignazio tnfsf14lightanoncanonicalnfkbstimulusinducesthehifpathway AT michaelbatie tnfsf14lightanoncanonicalnfkbstimulusinducesthehifpathway AT soniarocha tnfsf14lightanoncanonicalnfkbstimulusinducesthehifpathway |