Hypoxia-induced activation of HIF-1: Role of HIF-1α-Hsp90 interaction

Emmanuel Minet, Denis Mottet, Gaetan Michel, Isabelle Roland, Martine Raes, José Remacle, Carine Michiels

Research output: Contribution to journalArticlepeer-review


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-1α (HIF-1α), 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-1α 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-1α. Moreover, Hsp90 is not co-translocated with HIF-1α 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-1α activation. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)251-256
Number of pages6
JournalFEBS Letters
Issue number2
Publication statusPublished - 29 Oct 1999


  • Heat shock protein 90
  • Hypoxia
  • Hypoxia-inducible factor


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