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

International journal of molecular sciences (2020-04-30)
Laura D'Ignazio, Dilem Shakir, Michael Batie, H Arno Muller, Sonia Rocha
RÉSUMÉ

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.

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Sigma-Aldrich
IgG from mouse serum, reagent grade, ≥95% (SDS-PAGE), lyophilized powder
Sigma-Aldrich
Boc-Asn-OH, ≥98.5% (T)
Sigma-Aldrich
Anti-NFκB p52 Antibody, Upstate®, from mouse