Negative and positive regulation of HIF-1: a complex network

Hypoxia inducible factor-1 (HIF-1) is as a key transcriptional mediator of the hypoxic response in eukaryotic cells, regulating the expression of a myriad of genes involved in oxygen transport, glucose uptake and glycolysis and angiogenesis. Deregulation of HIF-1 activity occurs in many human cancers, usually at the level of the HIF-1alpha subunit. HIF-1 is regulated by a variety of mechanisms including transcription, translation post-translational modification, protein-protein interaction and degradation. Our understanding of the key signalling pathways that regulate HIF-1 has significantly progressed in recent years and has highlighted the potential for targeting the HIF-1 pathway as a basis for the development of new cancer therapies.