The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating Its Localisation,Stability, and Activity |
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| Authors: | Adam Albanese,Leonard A. Daly,Daniela Mennerich,Thomas Kietzmann,Violaine S e |
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| Affiliation: | 1.Department of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L697ZB, UK;2.Department of Biochemistry and System Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L697ZB, UK;3.Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland; (D.M.); (T.K.) |
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| 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. |
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| Keywords: | hypoxia, HIF-1α , HIF-2α , posttranslational modifications, phosphorylation, cysteine phosphorylation, methylation, acetylation, ubiquitination, sumoylation, S-nitrosylation, signalling |
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