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Schematic representation of HIF prolyl hydroxylases (PHDs) and factor-inhibiting HIF (FIH)) interplaying with E3 ligases and DUBs and their impact on HIF cellular abundance. Seven in absentia homologs ½ (SIAH1/2) and speckle-type POZ protein (SPOP) promote ubiquitylation of PHD1 and PHD3. So far, no E3 ligase is known for PHD2. Ankyrin repeat and SOCS box protein 4 (ASB4) and Otubain-1 (OTUB1) are hydroxylated by FIH.
