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

TY - JOUR

T1 - HIF-1β Positively Regulates NF-κB Activity via Direct Control of TRAF6

AU - D'Ignazio, Laura

AU - Shakir, Dilem

AU - Batie, Michael

AU - Muller, H. Arno

AU - Rocha, Sonia

PY - 2020/4/24

Y1 - 2020/4/24

N2 - 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.

AB - 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.

KW - ARNT

KW - Drosophila

KW - HIF

KW - NF-κB TRAF6

KW - TNF

UR - https://www.scopus.com/pages/publications/85084153578

U2 - 10.3390/ijms21083000

DO - 10.3390/ijms21083000

M3 - Article

C2 - 32344511

SN - 1661-6596

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 8

M1 - 3000

ER -