Nordic Life Science 1
THE OXYGEN-DEPENDENT SWITCHES PROLYL HYDROXYLATIO
N NORMOXIA O2 O2 O2 (3) OH OH VHL VHL OH (4) OH (2) PROTEASOMAL DEGRADATION HYPOXIA (1) HRE ARNT In hypoxia, the HIF complex binds to HRE elements in the genome, activating gene expression of gene products important for adaptation to low oxygen (1). Under high oxygen (normoxic) conditions, HIF is targeted for destruction by the proteasome (2), after being hydroxylated in an oxygen-dependent manner (3). This hydroxylation allows the HIF-1 protein to be recognized by the VHL complex (4). 52 NORDICLIFESCIENCE.ORG ILLUSTRATION MATTIAS KARLÉN/ANNIKI EDÉN