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2016 ; 4
(ä): 11
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Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability,
Localization, and Transactivity
#MMPMID26942179
Kietzmann T
; Mennerich D
; Dimova EY
Front Cell Dev Biol
2016[]; 4
(ä): 11
PMID26942179
show ga
The hypoxia-inducible factor ?-subunits (HIF?) are key transcription factors in
the mammalian response to oxygen deficiency. The HIF? regulation in response to
hypoxia occurs primarily on the level of protein stability due to
posttranslational hydroxylation and proteasomal degradation. However, HIF
?-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, HIF? regulating kinases are attractive therapeutic
targets. Although numerous kinases were reported to regulate HIF? indirectly,
direct phosphorylation of HIF? affects HIF? stability, nuclear localization, and
transactivity. Herein, we review the role of phosphorylation-dependent HIF?
regulation with emphasis on protein stability, subcellular localization, and
transactivation.