Fig. 2

Hydroxylation of HIF1A. In the presence of oxygen, HIF-1α is hydroxylated by PHD2. This hydroxylation is recognized by a protein complex containing Cullin 2, VHL, Elongin B, and Elongin C that targets HIF-1α for ubiquitination and leads to proteasome degradation of HIF1α. During EMT, the activation of TGF β decreases transcription of PHD2, which leads to the stabilization of HIF-1α. The stabilized HIF-1α binds to the hypoxia-response element (HRE) of the TWIST promoter along with HIF-1β to induce its transcription. (Blue arrowhead indicates sequential patterns. indicates inhibition. Purple arrowhead indicates translocation.)