Acetylation and Phosphorylation in the Regulation of Hypoxia-Inducible Factor Activities: Additional Options to Modulate Adaptations to Changes in Oxygen Levels.

O 2 is essential for the life of eukaryotic cells. The ability to sense oxygen availability and initiate a response to adapt the cell to changes in O 2 levels is a fundamental achievement of evolution. The key switch for adaptation consists of the transcription factors HIF1A, HIF2A and HIF3A. Their levels are tightly controlled by O 2 through the involvement of the oxygen-dependent prolyl hydroxylase domain-containing enzymes (PHDs/EGNLs), the von Hippel-Lindau tumour suppressor protein (pVHL) and the ubiquitin-proteasome system. Furthermore, HIF1A and HIF2A are also under the control of additional post-translational modifications (PTMs) that positively or negatively regulate the activities of these transcription factors. This review focuses mainly on two PTMs of HIF1A and HIF2A: phosphorylation and acetylation.