The stability and activity of HIF-1α are tightly regulated by oxygen levels. Under normoxia, prolyl hydroxylase enzymes hydroxylate HIF-1α, marking it for ubiquitination and subsequent degradation via the proteasome. In hypoxia, these hydroxylation reactions are inhibited, leading to the stabilization and accumulation of HIF-1α. This allows HIF-1α to dimerize with HIF-1β and activate transcription of target genes.
