Regulation of the Hypoxia-Inducible Factor-1α

摘要: Hypoxia-inducible factor-1 (HIF-1) is a master regulator of mammalian oxygen homeostasis. HIF-1 consists two subunits, HIF-1α and the aryl hydrocarbon receptor nuclear translocator (ARNT). Whereas hypoxia prevents ubiquitination proteasomal degradation ARNT expression thought to be oxygen-independent. We others previously showed that indispensable for DNA-binding transactivation function. To examine requirement accumulation translocation in hypoxia, we used ARNT-mutant mouse hepatoma ARNT-deficient embryonic stem cells. As shown by immunofluorescence, nucleus hypoxic cells did not require ARNT, demonstrating intrinsic During biochemical separation, both tend leak from nuclei absence corresponding subunit, suggesting heterodimerization required stable association within compartment. Nuclear stabilization heterodimer might also explain hypoxically increased total cellular levels observed some cell lines examined.