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HIF-1? restricts NF-?B-dependent gene expression to control innate immunity signals.


ABSTRACT: Hypoxia and inflammation are intimately linked. It is known that nuclear factor ?B (NF-?B) regulates the hypoxia-inducible factor (HIF) system, but little is known about how HIF regulates NF-?B. Here, we show that HIF-1? represses NF-?B-dependent gene expression. HIF-1? depletion results in increased NF-?B transcriptional activity both in mammalian cells and in the model organism Drosophila melanogaster. HIF-1? depletion enhances the NF-?B response, and this required not only the TAK-IKK complex, but also CDK6. Loss of HIF-1? results in an increased angiogenic response in mammalian cancer cells and increased mortality in Drosophila following infection. These results indicate that HIF-1? is required to restrain the NF-?B response, and thus prevents excessive and damaging pro-inflammatory responses.

SUBMITTER: Bandarra D 

PROVIDER: S-EPMC4314782 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals.

Bandarra Daniel D   Biddlestone John J   Mudie Sharon S   Müller H-Arno J HA   Rocha Sonia S  

Disease models & mechanisms 20141215 2


Hypoxia and inflammation are intimately linked. It is known that nuclear factor κB (NF-κB) regulates the hypoxia-inducible factor (HIF) system, but little is known about how HIF regulates NF-κB. Here, we show that HIF-1α represses NF-κB-dependent gene expression. HIF-1α depletion results in increased NF-κB transcriptional activity both in mammalian cells and in the model organism Drosophila melanogaster. HIF-1α depletion enhances the NF-κB response, and this required not only the TAK-IKK complex  ...[more]

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