Under normal oxygen conditions, HIF-1α is rapidly degraded by the ubiquitin-proteasome pathway. This degradation is mediated by prolyl hydroxylases which mark HIF-1α for ubiquitination. Under hypoxic conditions, prolyl hydroxylases are inactive, leading to the stabilization and accumulation of HIF-1α in the cell. This allows HIF-1α to translocate to the nucleus, where it dimerizes with HIF-1β and binds to hypoxia-response elements (HREs) in the promoters of target genes.
