The role of NF-kappaB in hypoxia-induced gene expression.
Hypoxia is a common physiologic and pathophysiologic stimulus that activates the expression of genes through oxygen-sensitive transcription factors including the hypoxia-inducible factor (HIF) and nuclear factor-kappaB (NF-kappaB). Hypoxia-dependent gene expression can have important physiologic or pathophysiologic consequences for an organism, depending upon the cause of the hypoxic insult. Consequently, this pathway represents an attractive therapeutic target in a number of disease states. While the mechanism linking hypoxia to the activation of HIF has been extensively studied, our understanding of how hypoxia activates NF-kappaB is limited. Recent studies have demonstrated that similar oxygen-sensing mechanisms are employed in conferring oxygen sensitivity to both HIF and NF-kappaB-dependent gene expression. Furthermore, there is an extensive degree of cross-talk occurring between NF-kappaB and HIF. Investigations into mechanisms of hypoxic activation of HIF and NF-kappaB and how these signaling pathways interact will uncover new therapeutic modalities in a diverse range of disease states where hypoxia is a feature of the microenvironment including cancer, vascular disease, and chronic inflammation.
Taylor
Cormac T
CT
UCD Conway Institute, School of Medicine and Medical Science, College of Life Science, University College Dublin, Belfield, Dublin, Ireland. cormac.taylor@ucd.ie
Cummins
Eoin P
EP
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D051793:Hypoxia-Inducible Factor 1; D016328:NF-kappa B