Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 29 June 2018 / Approved: 2 July 2018 / Online: 2 July 2018 (09:53:29 CEST)

A peer-reviewed article of this Preprint also exists.

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

Journal reference: Cells 2018, 7, 102
DOI: 10.3390/cells7080102

Abstract

Non-canonical NF-kB signalling plays important roles in development and function of the immune system but also is deregulated in a number of inflammatory diseases. Although, NF-kB and HIF crosstalk has been documented, this has only been described following canonical NF-kB 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-2a is induced at the transcriptional level following non-canonical NF-kB activation, via a mechanism dependent on the p52 subunit. Furthermore, we demonstrate that p52 can bind to the HIF-2a gene in cells. These results indicate that non-canonical NF-kB can lead to HIF signalling implicating HIF-2a as one of the downstream effectors of this pathway in cells.

Subject Areas

HIF; NF-kappaB; EPAS1; LIGHT; TNFSF14; p52; NIK; ChIP

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