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

Laura D'Ignazio, Dilem Shakir, Michael Batie, H. Arno Muller, Sonia Rocha (Lead / Corresponding author)

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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 Drosophila melanogaster. HIF-1β binds to the TRAF6 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.

Original languageEnglish
Article number3000
Pages (from-to)1-19
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume21
Issue number8
DOIs
Publication statusPublished - 24 Apr 2020

Keywords

  • ARNT
  • Drosophila
  • HIF
  • NF-κB TRAF6
  • TNF

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