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

Martina Minisini; Emanuele Cricchi; Claudio Brancolini

doi:10.3390/life14010020

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

Life (Basel). 2023 Dec 21;14(1):20. doi: 10.3390/life14010020.

Authors

Martina Minisini¹, Emanuele Cricchi¹, Claudio Brancolini¹

Affiliation

¹ Lab of Epigenomics, Department of Medicine, Università degli Studi di Udine, 33100 Udine, Italy.

Abstract

O₂ 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 O₂ 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 O₂ 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.

Keywords: HDACs; HIF-1 alpha; HIF-2 alpha; HIF-3 alpha; KATs; acetylation; hypoxia; phosphorylation.

Publication types

Review

Grants and funding

C.B.’s lab research activities were funded by Interreg Italia-Osterreich [ITAT11-018 SENECA] and by AIRC, under IG 2021-ID. 26200 project—P.I.