Preprint Article Version 1 This version is not peer-reviewed

HIF-1beta Positively Regulates NF-kappaB Activity via Direct Control of TRAF6

Version 1 : Received: 9 March 2020 / Approved: 10 March 2020 / Online: 10 March 2020 (11:14:37 CET)

A peer-reviewed article of this Preprint also exists.

D’Ignazio, L.; Shakir, D.; Batie, M.; Muller, H.A.; Rocha, S. HIF-1β Positively Regulates NF-κB Activity via Direct Control of TRAF6. Int. J. Mol. Sci. 2020, 21, 3000. D’Ignazio, L.; Shakir, D.; Batie, M.; Muller, H.A.; Rocha, S. HIF-1β Positively Regulates NF-κB Activity via Direct Control of TRAF6. Int. J. Mol. Sci. 2020, 21, 3000.

Journal reference: Int. J. Mol. Sci. 2020, 21, 3000
DOI: 10.3390/ijms21083000

Abstract

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

Subject Areas

NF-kappaB; HIF; ARNT; TRAF6; Transcription; ChIP; Drosophila

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