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Letter

Nature Cell Biology 6, 642–647 (1 July 2004) | doi:10.1038/ncb1144

HIF activation by pH-dependent nucleolar sequestration of VHL

Karim Mekhail , Lakshman Gunaratnam , Marie-Eve Bonicalzi & Stephen Lee

Hypoxia and acidosis occur in a wide variety of physiological and pathological settings that include muscle stress, tumour development and ischaemic disorders. A central element in the adaptive response to cellular hypoxia is HIF (hypoxia-inducible factor), a transcription factor that activates an array of genes implicated in oxygen homeostasis, tumour vascularization and ischaemic preconditioning.