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HIF-1? Positively Regulates NF-?B Activity via Direct Control of TRAF6.

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

SUBMITTER: D'Ignazio L

PROVIDER: S-EPMC7216149 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

D'Ignazio Laura L Shakir Dilem D Batie Michael M Muller H Arno HA Rocha Sonia S

International journal of molecular sciences 20200424 8

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 ...[more]

PMID: 32344511

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