Hypoxia‐induced activation of HIF‐1: role of HIF‐1α‐Hsp90 interaction

FEBS Letters

Minet, E¹  Michiels, C¹  Remacle, J¹  Raes, M¹  Michel, G²  Roland, I¹  Mottet, D¹ 

[1] Laboratoire de Biochimie et Biologie Cellulaire, Facultés Universitaires de la Paix, 61 rue de Bruxelles, 5000 Namur, Belgium;Laboratoire de Chimie Structurale, Facultés Universitaires de la Paix, 61 rue de Bruxelles, 5000 Namur, Belgium

关键词: Hypoxia;    Hypoxia-inducible factor;    Heat shock protein 90;    HIF-1;    hypoxia-inducible factor-1;    Hsp90;    heat shock protein 90;    Ahr;    aryl hydrocarbon receptor;    ARNT;    aryl hydrocarbon nuclear translocator;    bHLH;    basic helix loop helix;    PAS;    Per-ARNT-Sim;    HRE;    hypoxia responsive element;    HMEC-1;    human microvascular endothelial cells;   

DOI  :  10.1016/S0014-5793(99)01359-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown