Article (Scientific journals)
Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction.
Minet, E.; Mottet, Denis; Michel, G. et al.
1999In FEBS Letters, 460 (2), p. 251-6
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Keywords :
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
Abstract :
[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.
Disciplines :
Oncology
Biochemistry, biophysics & molecular biology
Author, co-author :
Minet, E.
Mottet, Denis ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Michel, G.
Roland, Isabelle 
Raes, M.
Remacle, Jean 
Michiels, C.
Language :
English
Title :
Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction.
Publication date :
1999
Journal title :
FEBS Letters
ISSN :
0014-5793
eISSN :
1873-3468
Publisher :
Elsevier Science, Amsterdam, Netherlands
Volume :
460
Issue :
2
Pages :
251-6
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
IRSIA - Institut pour l'Encouragement de la Recherche Scientifique dans l'Industrie et l'Agriculture [BE]
BELSPO - Service Public Fédéral de Programmation Politique scientifique [BE]
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