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
|Author:||Kietzmann, Thomas1; Mennerich, Daniela1; Dimova, Elitsa Y.1|
1Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Finland
|Online Access:||PDF Full Text (PDF, 1.1 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201710098934
|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.
Frontiers in cell and developmental biology
|Type of Publication:||
A2 Review article in a scientific journal
|Field of Science:||
1182 Biochemistry, cell and molecular biology
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 © 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.