Fig. 2: The multifaceted relationship among hypoxia, PHD enzymes and HIF factors in supporting or restraining tumor growth.

Hypoxia can regulate other enzymes of the 2-OGDD family, besides the PHDs and FIH. Different mechanisms can regulate the activity of the PHD enzymes, including the presence of binding partners, the metabolic status of the cell and specific post-translational modifications (PTM). The HIF proteins are the main targets of PHDs, but several alternative targets have been described, including p53, AKT1, BRD4 and DYRK1, holding the possibility to influence tumor behaviour. Finally, a number of pro-oncogenic signals have been shown to stabilize the HIF-α subunit in a oxygen-independent way. Created in https://BioRender.com.