Fig. 1. Dual role of HIF in regulating cell survival and cell death, depending on P_O2 and HIF- protein levels. The HIF system transactivates an extended physiological pathway, encompassing a wide array of physiological responses to hypoxia, ranging from mechanisms that increase cell survival to those inducing cell cycle arrest or even apoptosis. Depending on the degree and duration of hypoxia, quantitative and qualitative changes in the hypoxia response occur that may be regulated by concomitant changes in HIF- protein levels, modifications and HIF- subunit expression.