Reference : Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Oncology
http://hdl.handle.net/2268/29053
Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction.
English
Minet, E. [> > > >]
Mottet, Denis mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Michel, G. [> > > >]
Roland, Isabelle [> > > >]
Raes, M. [> > > >]
Remacle, Jean [> > > >]
Michiels, C. [> > > >]
1999
FEBS Letters
Elsevier Science
460
2
251-6
Yes (verified by ORBi)
International
0014-5793
Amsterdam
The Netherlands
[en] Animals ; Anoxia/metabolism ; COS Cells ; Cell Line ; DNA-Binding Proteins/metabolism ; Endothelium, Vascular ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; Microscopy, Fluorescence ; Molecular Chaperones ; Nuclear Proteins/metabolism ; Protein Binding ; Time Factors ; Transcription Factors/metabolism ; Transcription, Genetic ; Transfection
[en] The protein chaperone heat shock protein 90 (Hsp90) is a major regulator of different transcription factors such as MyoD, a basic helix loop helix (bHLH) protein, and the bHLH-Per-aryl hydrocarbon nuclear translocator (ARNT)-Sim (PAS) factors Sim and aryl hydrocarbon receptor (Ahr). The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha), involved in the response to hypoxia, also belongs to the bHLH-PAS family. This work was aimed to investigate the putative role of Hsp90 in HIF-1 activation by hypoxia. Using a EGFP-HIF-1alpha fusion protein, co-immunoprecipitation experiments evidenced that the chimeric protein expressed in COS-7 cells interacts with Hsp90 in normoxia but not in hypoxia. We also demonstrated that Hsp90 interacts with the bHLH-PAS domain of HIF-1alpha. Moreover, Hsp90 is not co-translocated with HIF-1alpha into the nucleus. At last, we showed that Hsp90 activity is essential for HIF-1 activation in hypoxia since it is inhibited in the presence of geldanamycin. These results indicate that Hsp90 is a major regulator in HIF-1alpha activation.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Fonds National de Recherche pour l'Industrie et l'Agriculture ; Politique Scientifique Fédérale (Belgique) = Belgian Federal Science Policy
http://hdl.handle.net/2268/29053

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