Hypoxia-Inducible Factors (HIFs)

Hypoxia-inducible factors (HIFs) are transcription factors that play a critical role in cellular adaptation to low oxygen conditions (hypoxia). They regulate the expression of genes involved in angiogenesis, glucose metabolism, cell survival, and erythropoiesis. HIFs are heterodimers consisting of an oxygen-sensitive alpha subunit (e.g., HIF-1alpha, HIF-2alpha) and a constitutively expressed beta subunit (HIF-1beta). Under normoxic conditions, HIF-alpha subunits are hydroxylated by prolyl hydroxylases (PHDs), leading to their ubiquitination and proteasomal degradation. In hypoxia, PHDs are inhibited, resulting in HIF-alpha stabilization, dimerization with HIF-1beta, and translocation to the nucleus, where they bind to hypoxia response elements (HREs) in the promoters of target genes.

Other names

HIF-1HIF-2HIF-alphaHIF1AHIF2A

HIF inhibitors block the transcriptional activity of HIFs by preventing DNA binding or interfering with HIF subunit dimerization. PHIs stabilize HIF-alpha subunits at normal oxygen levels.