Fig. 3.

Cellular response in normoxic, acute, intermittent, and chronic hypoxic conditions. HIF proteins are constitutively expressed, but under normal oxygen concentration are quickly ubiquitinated and degraded under the control of VHL. Under acute hypoxia, HIF-1α levels are stabilized and can translocate to the nucleus where they can bind with HIF-1β. With the aid of cofactor p300 gene expression can be induced for the genes involved in acute hypoxic response. Under intermittent hypoxia, HIF-2α levels stabilize alongside HIF-1α levels. Under chronic hypoxia, HIF-1α levels dissipate and HIF-2α levels stabilize. HIF-2α is then the primary cause of gene transcription in chronic hypoxia