HIF-1 (hypoxia-inducible factor-1), a transcription factor involved in homeostasis of oxygen concentration, upregulates gene expression in processes of glycolysis, cell proliferation and apoptosis, angiogenesis, and contributes to mammalian organism hypoxia adaptation, embryo development, various ischemic diseases and tumors. The regulation of HIF-1 activity is the focus of hypoxia responsive genes expression. The regulation occurs dominantly at the two divergent signaling pathways rooting from Ras, transactivation mediated by Ras/Raf/MEK pathway and PI(3)K/Akt dependent stabilization of HIF-1alpha protein, cooperatively but independently regulates the activity of HIF.