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

Laura D'Ignazio; Michael Batie; Sonia Rocha

doi:10.3390/cells7080102

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

Laura D'Ignazio
, Michael Batie
, Sonia Rocha (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

261 Downloads (Pure)

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.

Original language	English
Article number	102
Pages (from-to)	1-14
Number of pages	14
Journal	Cells
Volume	7
Issue number	8
DOIs	https://doi.org/10.3390/cells7080102
Publication status	Published - 8 Aug 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

HIF
NF-κb
EPAS1
LIGHT
TNFSF14
p52
NIK
ChIP

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10.3390/cells7080102Licence: CC BY

Final Published VersionFinal published version, 2.02 MBLicence: CC BY

Cite this

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

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.",

keywords = "HIF, NF-κb, EPAS1, LIGHT, TNFSF14, p52, NIK, ChIP",

author = "Laura D'Ignazio and Michael Batie and Sonia Rocha",

note = "Funding: This work was funded by CRUK Senior Fellowship to SR (C99667/A12918), a Wellcome Trust Strategic Award (097945/B/11/Z), a Wellcome Trust PhD studentship to LDI, and by the University of Liverpool.",

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doi = "10.3390/cells7080102",

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T1 - TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway

AU - D'Ignazio, Laura

AU - Batie, Michael

AU - Rocha, Sonia

N1 - Funding: This work was funded by CRUK Senior Fellowship to SR (C99667/A12918), a Wellcome Trust Strategic Award (097945/B/11/Z), a Wellcome Trust PhD studentship to LDI, and by the University of Liverpool.

PY - 2018/8/8

Y1 - 2018/8/8

N2 - 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.

AB - 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.

KW - HIF

KW - NF-κb

KW - EPAS1

KW - LIGHT

KW - TNFSF14

KW - p52

KW - NIK

KW - ChIP

U2 - 10.3390/cells7080102

DO - 10.3390/cells7080102

M3 - Article

C2 - 30096845

SN - 2073-4409

VL - 7

SP - 1

EP - 14

JO - Cells

JF - Cells

IS - 8

M1 - 102

ER -

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

Abstract

UN SDGs

Keywords

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