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)

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)
    104 Downloads (Pure)

    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
    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

    ASJC Scopus subject areas

    • Catalysis
    • Molecular Biology
    • Spectroscopy
    • Computer Science Applications
    • Physical and Theoretical Chemistry
    • Organic Chemistry
    • Inorganic Chemistry

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