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.
UCD Conway Institute, School of Medicine and Medical Science, College of Life Science, University College Dublin, Belfield, Dublin, Ireland. cormac.taylor@ucd.ie
Cormac T
CT
Taylor
Eoin P
EP
Cummins
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