Abstract
The transcriptional response to hypoxia is primarily mediated by two hypoxia-inducible factors – HIF-1α and HIF-2α. 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-α subunits, including effects on the Notch and c-Myc pathways, contribute to their distinct functions. HIF-2α transcriptional targets include genes involved in erythropoiesis, angiogenesis, metastasis, and proliferation. Therefore, HIF-2α contributes significantly to both normal physiology as well as tumorigenesis. Here, we summarize the function of HIF-2α during development as well as its contribution to pathologic conditions, such as tumors and vascular disease.
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Abbreviations
- ARNT:
-
aryl hydrocarbon receptor nuclear translocator
- Epo:
-
erythropoietin
- HIFs:
-
hypoxia-inducible factors
- HRE:
-
hypoxia response element
- IRE:
-
iron response element
- IRP:
-
iron regulatory protein
- LOX:
-
lysyl oxidase
- PAS:
-
Per-ARNT-Sim
- pVHL:
-
von Hippel–Lindau
- RCC:
-
renal clear cell carcinoma
- TGF-α:
-
transforming growth factor-α
- TAD:
-
transcriptional activation domain
- UTR:
-
untranslated region
- VEGF:
-
vascular endothelial growth factor
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Patel, S., Simon, M. Biology of hypoxia-inducible factor-2α in development and disease. Cell Death Differ 15, 628–634 (2008). https://doi.org/10.1038/cdd.2008.17
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