Transactivation and Inhibitory Domains of Hypoxia-inducible Factor 1α MODULATION OF TRANSCRIPTIONAL ACTIVITY BY OXYGEN TENSION

摘要: Hypoxia-inducible factor 1 (HIF-1) binds to cis-acting hypoxia-response elements within the erythropoietin, vascular endothelial growth factor, and other genes activate transcription in hypoxic cells. HIF-1 is a basic helix-loop-helix composed of HIF-1alpha HIF-1beta subunits. Here, we demonstrate that contains two transactivation domains located between amino acids 531 826. When expressed as GAL4 fusion proteins, transcriptional activity these increased response hypoxia. Fusion protein levels were unaffected by changes cellular O2 tension. Two minimal localized acid residues 531-575 786-826. The activation separated sequences inhibited transactivation. Deletion analysis demonstrated gradual removal inhibitory domain (amino 576-785) was associated with progressively especially cells cultured at 20% O2. Transcriptional GAL4/HIF-1alpha proteins exposed 1% O2, cobalt chloride, or desferrioxamine, each which also endogenous but did not affect levels. These results indicate mediated from both domains.