Figure 3.

Regulation of HIF and NF‐κB. (A) Regulation of HIF in hypoxic and normoxic conditions. In hypoxic conditions, HIF‐α stabilizes and forms a complex with HIF‐β. This HIF complex translocates to the nucleus, binds to hypoxia response elements (HREs), and activates genes that help the cell adapt to low oxygen. HIF‐α is hydroxylated by prolyl hydroxylases (PHDs) under normoxic conditions. The hydroxylated HIF‐α is then catalyzed by the von Hippel–Lindau (VHL) protein, leading to its subsequent degradation through the proteasome pathway. (B) The canonical activation process of NF‐κB. NF‐κB is located in the cytoplasm and binds with the inhibitory protein IκBα. When IκB kinase (IKK) is activated, the IκBα is phosphorylated and degraded via the ubiquitination pathway. With the degradation of IκBα, the p50, and RelA dimer translocates to the nucleus, where it activates the transcription of multiple target genes. HIF, hypoxia‐inducible factor; NF‐κB, nuclear factor kappa‐B.