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Kietzmann T, Mennerich D, Dimova EY. Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity. Front Cell Dev Biol. 2016;4:11doi: 10.3389/fcell.2016.00011.
Kietzmann, T., Mennerich, D., & Dimova, E. Y. (2016). Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity. Frontiers in cell and developmental biology, 411. https://doi.org/10.3389/fcell.2016.00011
Kietzmann, Thomas, et al. "Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity." Frontiers in cell and developmental biology vol. 4 (2016): 11. doi: https://doi.org/10.3389/fcell.2016.00011
Kietzmann T, Mennerich D, Dimova EY. Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity. Front Cell Dev Biol. 2016 Feb 23;4:11. doi: 10.3389/fcell.2016.00011. eCollection 2016. PMID: 26942179; PMCID: PMC4763087.
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Front Cell Dev Biol. 2016 Feb 23;4:11. doi: 10.3389/fcell.2016.00011. eCollection 2016.

Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity.

Frontiers in cell and developmental biology

Thomas Kietzmann, Daniela Mennerich, Elitsa Y Dimova

Affiliations

  1. Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu Finland.

PMID: 26942179 PMCID: PMC4763087 DOI: 10.3389/fcell.2016.00011

Abstract

The hypoxia-inducible factor α-subunits (HIFα) are key transcription factors in the mammalian response to oxygen deficiency. The HIFα regulation in response to hypoxia occurs primarily on the level of protein stability due to posttranslational hydroxylation and proteasomal degradation. However, HIF α-subunits also respond to various growth factors, hormones, or cytokines under normoxia indicating involvement of different kinase pathways in their regulation. Because these proteins participate in angiogenesis, glycolysis, programmed cell death, cancer, and ischemia, HIFα regulating kinases are attractive therapeutic targets. Although numerous kinases were reported to regulate HIFα indirectly, direct phosphorylation of HIFα affects HIFα stability, nuclear localization, and transactivity. Herein, we review the role of phosphorylation-dependent HIFα regulation with emphasis on protein stability, subcellular localization, and transactivation.

Keywords: HIF-1α; MAPK pathway; PI3K/PKB pathway; hypoxia; kinase; phosphorylation

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