Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating its Localisation, Stability and Activity

Version 1 : Received: 3 December 2020 / Approved: 4 December 2020 / Online: 4 December 2020 (13:45:45 CET)

A peer-reviewed article of this Preprint also exists.

Albanese, A.; Daly, L.A.; Mennerich, D.; Kietzmann, T.; Sée, V. The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating Its Localisation, Stability, and Activity. Int. J. Mol. Sci. 2021, 22, 268. Albanese, A.; Daly, L.A.; Mennerich, D.; Kietzmann, T.; Sée, V. The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating Its Localisation, Stability, and Activity. Int. J. Mol. Sci. 2021, 22, 268.

Journal reference: Int. J. Mol. Sci. 2020, 22, 268
DOI: 10.3390/ijms22010268

Abstract

The hypoxia signalling pathway enables adaptation of cells to decreased oxygen availability. When oxygen becomes limiting, the central transcription factors of the pathway, hypoxia-inducible factors (HIFs), are stabilised and activated to induce the expression of hypoxia-regulated genes, thereby maintaining cellular homeostasis. Whilst hydroxylation has been thoroughly described as the major and canonical modification of the HIF-α subunits, regulating both HIF stability and activity, a range of other post-translational modifications decorating the entire protein play also a crucial role in altering HIF localisation, stability, and activity. These modifications, their conservation throughout evolution and their effects on HIF-dependent signalling are discussed in this review.

Subject Areas

Hypoxia; HIF-1α; HIF-2α; Posttranslational modifications; Phosphorylation; Acetylation; Ubiquitination; Sumoylation; S-Nitrosylation; Signalling; cystein phosphorylation; methylation

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