Figure 2.

Cellular response to hypoxia: Levels of Hypoxia Inducible Factor-1 (HIF-1) are regulated by cellular oxygen by proline hydroxylation. The reaction is catalyzed by the enzymes prolyl 4-hydroxylases. Under normoxia (blue arrows), the intracellular level of HIF-1α is kept low by rapid ubiquitination and subsequent proteasomal degradation via recruitment of von Hippel–Lindau protein (pVHL), which depend on the hydroxylation of proline residues. In contrast, under hypoxia (orange arrows), both the intracellular level and the transcriptional activity of HIF-1α increase as a result of suppressed PHD activities. Consequently, HIF-1α forms a heterodimer with HIF-1β and changes the transcriptional rates of HIF-1-regulated genes under hypoxia; Reproduced with permission from # 7.