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First published online 1 August 2006
doi: 10.1242/jcs.03069

Journal of Cell Science 119, 3351-3362 (2006)
Published by The Company of Biologists 2006
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Research Article

Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under hypoxia through elevated p53 protein level

Antoine Hubert, Sébastien Paris, Jean-Pascal Piret, Noëlle Ninane, Martine Raes and Carine Michiels*

Laboratory of Biochemistry and Cellular Biology, University of Namur, 61 Rue de Bruxelles, 5000 Namur, Belgium

* Author for correspondence (e-mail: carine.michiels{at}fundp.ac.be)

Accepted 25 May 2006

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{alpha} 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{alpha} protein level, indicating a regulation of its transcriptional activity. Similar results were obtained using CK2{alpha} 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-{alpha}. Since CK2 activity is increased in hypoxic conditions, this process provides one more mechanism to ensure enhanced HIF-1 activity under such conditions.

Key words: Hypoxia, HIF-1, p53, CK2, Transcription regulation, MDM2


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[Abstract] [Full Text] [PDF]


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