University of Oulu

Kietzmann T, Mennerich D and Dimova EY (2016) Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity. Front. Cell Dev. Biol. 4:11. doi: 10.3389/fcell.2016.00011

Hypoxia-inducible factors (HIFs) and phosphorylation : impact on stability, localization, and transactivity

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Author: Kietzmann, Thomas1; Mennerich, Daniela1; Dimova, Elitsa Y.1
Organizations: 1Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
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Language: English
Published: Frontiers Media, 2016
Publish Date: 2017-10-09


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.

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Series: Frontiers in cell and developmental biology
ISSN: 2296-634X
ISSN-E: 2296-634X
ISSN-L: 2296-634X
Volume: 4
Issue: 11
DOI: 10.3389/fcell.2016.00011
Type of Publication: A2 Review article in a scientific journal
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: Work in the authors' laboratory was supported by grants from the Academy of Finland, the Sigrid Juselius Foundation, Jane and Aatos Erkko Foundation, and Biocenter Oulu.
Copyright information: Copyright © 2016 Kietzmann, Mennerich and Dimova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.