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Title: Casein kinase 2 inhibition decreases hypoxia inducible factor-1 activity under hypoxia through elevated p53 protein level
Authors: Hubert, Antoine
Paris, Sébastien
Michiels, Carine # ×
Issue Date: 15-Aug-2006
Publisher: Co. of Biologists
Series Title: Journal of Cell Science vol:119 issue:16 pages:3351-3362
Abstract: HIF-1 (hypoxia-inducible factor-1) is the main
transcription factor involved in the adaptation of cells to
hypoxia. In addition to regulation of HIF-1 protein level,
HIF-1 activity is also enhanced by several pathways
involving asparagine hydroxylation and phosphorylation.
Here, we investigated the relationship between casein
kinase 2 (CK2), p53 and HIF-1. An increase in p53 protein
level and transcriptional activity was observed when CK2
was inhibited by different inhibitors under normoxia and
hypoxia. This increase was in parallel with a decrease in
HIF-1 activity without changes in HIF-1 protein level,
indicating a regulation of its transcriptional activity.
Similar results were obtained using CK2 siRNA. Ectopic
overexpression of p53 also led to an inhibition of HIF-1
activity. Conversely, CK2 inhibition had no effect in p53-
null cells indicating that the inhibitory effect of CK2
inhibitors requires the presence of p53. p53 activity was not
required because overexpression of a p53 mutated in its
DNA-binding domain exerted the same effect as wild-type
p53 and because the effect of CK2 inhibitors was still
observed when p53 activity was inhibited by pifithrin-.
Since CK2 activity is increased in hypoxic conditions, this
process provides one more mechanism to ensure enhanced
HIF-1 activity under such conditions.
ISSN: 0021-9533
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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