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Cited by 176Cancer, Hypoxia, and MetabolismErythropoietin and Anemia TreatmentKruppel-like factors research

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

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Kietzmann, Thomas, Mennerich, Daniela, Dimova, Elitsa Y.·2016·Frontiers in Cell and Developmental Biology
DOI 10.3389/fcell.2016.00011PMC PMC4763087
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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.

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  • HIFs are direct substrates of a variety of protein kinases that regulate HIF stabilization, nuclear translocation, and activation.

    “HIFs are direct substrates of a variety of protein kinases that regulate HIF stabilization, nuclear translocation, and activation (Kietzmann et al., 2016).”

    From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Kietzmann et al., 2016

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Authors
Kietzmann, T., Mennerich, D., & Dimova, E. Y.
Affiliations
University of Oulu (FI)
Corresponding author
Kietzmann, Thomas
ORCID
Venue
Frontiers in Cell and Developmental Biology
Publisher
Frontiers Media SA
Published
2016-02-23
Volume
4
Pages
11-11
ISSN
2296-634X (ISSN-L)
DOI
10.3389/fcell.2016.00011
PMC
PMC4763087
OpenAlex
W2300955327
Cited by
176
References
167
Citations by year
2026: 7 · 2025: 11 · 2024: 16 · 2023: 22 · 2022: 23 · 2021: 17 · 2020: 26 · 2019: 24 · 2018: 16 · 2017: 6 · 2016: 7
FWCI
1.62
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Suomen Akatemia
  • Sigrid Juséliuksen Säätiö
  • Jane ja Aatos Erkon Säätiö
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
Keywords
hypoxia-inducible factor alpha, protein stability, proteasomal degradation, nuclear localization, transcriptional activation, kinase regulation, angiogenesis, glycolysis, cancer, ischemia

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