HIF-1β Positively Regulates NF-κB Activity via Direct Control of TRAF6

D'Ignazio, Laura, Shakir, Dilem, Batie, Michael ORCID: 0000-0002-7508-6641, Muller, H Arno and Rocha, Sonia (2020) HIF-1β Positively Regulates NF-κB Activity via Direct Control of TRAF6. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (8). E3000-.

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Official URL: http://dx.doi.org/10.3390/ijms21083000

Abstract

NF-κB signalling is crucial for cellular responses to inflammation but is also associated with the hypoxia response. NF-κB and hypoxia inducible factor (HIF) transcription factors possess an intense molecular crosstalk. Although it is known that HIF-1α modulates NF-κB transcriptional response, very little is understood regarding how HIF-1β contributes to NF-κB signalling. Here, we demonstrate that HIF-1β is required for full NF-κB activation in cells following canonical and non-canonical stimuli. We found that HIF-1β specifically controls TRAF6 expression in human cells but also in <i>Drosophila melanogaster</i>. HIF-1β binds to the <i>TRAF6</i> gene and controls its expression independently of HIF-1α. Furthermore, exogenous TRAF6 expression is able to rescue all of the cellular phenotypes observed in the absence of HIF-1β. These results indicate that HIF-1β is an important regulator of NF-κB with consequences for homeostasis and human disease.

Item Type:	Article
Uncontrolled Keywords:	NF-kappa B TRAF6, HIF, ARNT, Drosophila, TNF
Depositing User:	Symplectic Admin
Date Deposited:	11 May 2020 10:31
Last Modified:	25 Jan 2024 12:58
DOI:	10.3390/ijms21083000
Open Access URL:	https://www.mdpi.com/1422-0067/21/8/3000
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3086503