Article (Scientific journals)
Role for casein kinase 2 in the regulation of HIF-1 activity.
Mottet, Denis; Ruys, Sebastien Pyr Dit; Demazy, Catherine et al.
2005In International Journal of Cancer, 117 (5), p. 764-74
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Keywords :
Casein Kinase II/antagonists & inhibitors/metabolism; Cell Hypoxia; Cell Line, Tumor; Colorimetry; Enzyme Inhibitors/pharmacology; Fluorescent Antibody Technique; Humans; Transcription, Genetic/physiology; Vascular Endothelial Growth Factor A/metabolism
Abstract :
[en] Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that plays a major role in cellular adaptation to hypoxia. The mechanisms regulating HIF-1 activity occurs at multiple levels in vivo. The HIF-1alpha subunit is highly sensible to oxygen and is rapidly degraded by the proteasome 26S in normoxia. Activation in hypoxia occurs through a multistep process including inhibition of HIF-1alpha degradation, but also increase in the transactivation activity of HIF-1. Several data indicate that phosphorylation could play a role in this regulation. In this report, we investigated the role of casein kinase 2 (CK2), an ubiquitous serine/threonine kinase, in the regulation of HIF-1 activity. Hypoxia was capable of increasing the expression of the beta subunit of CK2, of inducing a relocalization of this subunit at the plasma membrane, of inducing nuclear translocation of the alpha subunit and of increasing CK2 activity. Three inhibitors of this kinase, DRB (5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole), TBB (4,5,6,7-tetrabromotriazole) and apigenin, as well as overexpression of a partial dominant negative mutant of CK2alpha, were shown to inhibit HIF-1 activity as measured by a reporter assay and through hypoxia-induced VEGF and aldolase expression. This does not occur at the stabilization process since they did not affect HIF-1alpha protein level. DNA-binding activity was also not inhibited. We conclude that CK2 is an important regulator of HIF-1 transcriptional activity but the mechanism of this regulation remains to be determined. Since HIF-1 plays a major role in tumor angiogenesis and since CK2 has been described to be overexpressed in tumor cells, this new pathway of regulation can be one more way for tumor cells to survive.
Disciplines :
Biochemistry, biophysics & molecular biology
Oncology
Author, co-author :
Mottet, Denis ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Ruys, Sebastien Pyr Dit
Demazy, Catherine
Raes, Martine
Michiels, Carine
Language :
English
Title :
Role for casein kinase 2 in the regulation of HIF-1 activity.
Publication date :
2005
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
Volume :
117
Issue :
5
Pages :
764-74
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique
Commentary :
Copyright 2005 Wiley-Liss, Inc
Available on ORBi :
since 24 November 2009

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