Biology of hypoxia-inducible factor-2alpha in development and disease.
The transcriptional response to hypoxia is primarily mediated by two hypoxia-inducible factors--HIF-1alpha and HIF-2alpha. While these proteins are highly homologous, increasing evidence suggests they have unique transcriptional targets and differential impact on tumor growth. Furthermore, non-transcriptional effects of the HIF-alpha subunits, including effects on the Notch and c-Myc pathways, contribute to their distinct functions. HIF-2alpha transcriptional targets include genes involved in erythropoiesis, angiogenesis, metastasis, and proliferation. Therefore, HIF-2alpha contributes significantly to both normal physiology as well as tumorigenesis. Here, we summarize the function of HIF-2alpha during development as well as its contribution to pathologic conditions, such as tumors and vascular disease.
Patel
S A
SA
Department of Cell and Developmental Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Simon
M C
MC
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D014018:Tissue Distribution; D014158:Transcription, Genetic; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1