[HTML][HTML] Erythrocytosis and pulmonary hypertension in a mouse model of human HIF2A gain of function mutation
Q Tan, H Kerestes, MJ Percy, R Pietrofesa… - Journal of Biological …, 2013 - ASBMB
The central pathway for oxygen-dependent control of red cell mass is the prolyl hydroxylase
domain protein (PHD): hypoxia inducible factor (HIF) pathway. PHD site specifically prolyl
hydroxylates the transcription factor HIF-α, thereby targeting the latter for degradation. Under
hypoxia, this modification is attenuated, allowing stabilized HIF-α to activate target genes,
including that for erythropoietin (EPO). Studies employing genetically modified mice point to
Hif-2α, one of two main Hif-α isoforms, as being the critical regulator of Epo in the adult …
domain protein (PHD): hypoxia inducible factor (HIF) pathway. PHD site specifically prolyl
hydroxylates the transcription factor HIF-α, thereby targeting the latter for degradation. Under
hypoxia, this modification is attenuated, allowing stabilized HIF-α to activate target genes,
including that for erythropoietin (EPO). Studies employing genetically modified mice point to
Hif-2α, one of two main Hif-α isoforms, as being the critical regulator of Epo in the adult …