Background:
PHD2 protein catalyzes the posttranslational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. In the presence of oxygen, PHD2 converts specific prolyl residues in HIF alpha to hydroxyproline, leading to HIF alpha proteasomal degradation via the von Hippel-Lindau ubiquitylation complex. Low oxygen levels, sensed at the cellular level, cause the HIF conversion to be reduced so that HIF levels are stable. This results in increased angiogenesis as HIF1 alpha regulates the expression of many angiogenesis-related genes.