A tale of two transcription factors: NF-kB and HIF crosstalk

Hypoxia-inducible factor is a key transcriptional factor involved in the cellular response to low levels of oxygen, hypoxia. Moreover, hypoxia-inducible factor has been recently associated with a role in inflammation and immunity. Importantly, hypoxia-inducible factor is regulated by the major inflammatory responsive transcription factor, nuclear factor-?B. These two major pathways have been intimately linked. On one hand, they share a number of common target genes; on the other hand, physical interactions between hypoxia-inducible factor subunits and nuclear factor-?B have been observed. Even though the role of nuclear factor-?B over hypoxia-inducible factor is fairly well-known, the involvement of hypoxia-inducible factor over the nuclear factor-?B pathway is not. Given the overlap between these pathways, it would not be surprising to find a functional involvement of hypoxia-inducible factor in processes where nuclear factor-?B is involved. In this review, we will describe the communalities between hypoxia-inducible factor and nuclear factor-?B pathways, highlighting the crosstalk that occurs in a variety of conditions. Taken together all the communalities between hypoxia-inducible factor and nuclear factor-?B pathways, there is no doubt that a crosstalk occurs, which can potentially bring new insights for therapeutic intervention in situations of disease such as cancer, stroke or rheumatoid arthritis.