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FEBS Lett. 1999 Oct 29;460(2):251-6.

Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction.

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  • 1Laboratoire de Biochimie et Biologie Cellulaire, Facult├ęs Universitaires de la Paix, 61 rue de Bruxelles, 5000, Namur, Belgium. emmanuel.minet@fundp.ac.be

Abstract

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.

PMID:
10544245
[PubMed - indexed for MEDLINE]
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