HIF/HIF Prolyl-Hydroxylase

Hypoxia-inducible factor (HIF) prolyl-hydroxylase is a key enzyme that regulates the stability of HIF, a transcription factor critical for cellular response to oxygen levels. Under normal oxygen conditions, prolyl-hydroxylase hydroxylates specific proline residues on HIF, marking it for degradation via the ubiquitin-proteasome pathway. This hydroxylation depends on oxygen, iron, and 2-oxoglutarate as co-substrates, making the enzyme an effective oxygen sensor. Under hypoxic conditions, the activity of prolyl-hydroxylase decreases, leading to the stabilization and accumulation of HIF, which then translocates to the nucleus and activates the transcription of genes involved in angiogenesis, metabolism, and survival strategies, facilitating adaptation to low-oxygen environments.