Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1): heterodimerization with ARNT is not necessary for nuclear accumulation of HIF-1alpha.

摘要: Hypoxia-inducible factor-1 (HIF-1) is a master regulator of mammalian oxygen homeostasis. HIF-1 consists two subunits, HIF-1alpha and the aryl hydrocarbon receptor nuclear translocator (ARNT). Whereas hypoxia prevents proteasomal degradation HIF-1alpha, ARNT expression thought to be oxygen-independent. We others previously showed that indispensable for DNA-binding transactivation function. Here, we have used ARNT-mutant mouse hepatoma embryonic stem cells examine requirement accumulation translocation in hypoxia. As shown by immunofluorescence, nucleus hypoxic was independent presence ARNT, suggesting intrinsic HIF-1alpha. Co-immunoprecipitation together with could performed extracts but not cytosolic fractions, implying formation complex occurs nucleus. A proteasome inhibitor thiol-reducing agent mimic inducing nucleus, indicating escape from proteolytic sufficient During biochemical separation, both tend leak nuclei absence either subunit, heterodimerization required stable association within compartment. Nuclear stabilization heterodimer might also explain hypoxically increased total cellular levels observed some cell lines examined.