How does HIF respond to oxygen?
HIF-1 was found to decrease oxygen consumption in these cells by inhibiting C-MYC, a transcription factor that regulates mitochondrial mass and oxygen consumption and is known to be down-regulated in a variety of human cancers.
What does hypoxia-inducible factor do?
HIF-1, when stabilized by hypoxic conditions, upregulates several genes to promote survival in low-oxygen conditions. These include glycolysis enzymes, which allow ATP synthesis in an oxygen-independent manner, and vascular endothelial growth factor (VEGF), which promotes angiogenesis.
How is HIF-1 regulated?
Under normal oxygen tension, HIF-1α protein expression is negatively regulated by proteasomal degradation and ubiquitination in a pathway involving von Hippel−Lindau protein (pVHL), a tumor suppressor protein and one of the recognized components of an E3 ubiquitin protein ligase27.
How does HIF regulate transcription?
Upon hypoxia, the HIF alpha subunits are stabilized and accumulate in the nucleus, where they dimerize with HIF1B, allowing them to bind to DNA and stimulate the transcription of their target genes.
What does HIF pathway do?
Hypoxia-inducible factor (HIF) is an alpha,beta-heterodimeric transcription factor that mediates cellular responses to low oxygen concentration via the transcriptional activation of specific genes involved in both tumorogenesis and angiogenesis.
How does HIF increase performance through angiogenesis?
The target genes of HIF-1 increase oxygen transport through mechanisms such as erythropoietin-mediated erythropoiesis and vascular endothelial growth factor-induced angiogenesis and improve tissue function during low oxygen availability through increased expression of glucose transporters and glycolytic enzymes, which …
How does HIF regulate erythropoiesis in normoxic conditions?
Recent experimental evidence suggests that HIF promotes erythropoiesis through coordinated cell type-specific hypoxia responses, which include increased EPO production in the kidney and liver, enhanced iron uptake and utilization, as well as changes in the bone marrow microenvironment that facilitate erythroid …
What role does EPO play in erythropoiesis?
Erythropoietin (EPO) is the key hormone responsible for effective erythropoiesis, and iron is the essential mineral required for hemoglobin production. EPO allows survival and proliferation of erythroid precursor cells by generating intracellular signals resulting in the prevention of apoptosis.