The role of hypoxia-inducible factor post-translational modifications in regulating its localisation, stability, and activity

Abstract

The hypoxia signalling pathway enables adaptation of cells to decreased oxygen availa-bility. 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 de-scribed 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 conser-vation throughout evolution, and their effects on HIF-dependent signalling are discussed in this review.