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Hypoxia‐induced activation of HIF‐1: role of HIF‐1α‐Hsp90 interaction
Author(s) -
Minet E,
Mottet D,
Michel G,
Roland I,
Raes M,
Remacle J,
Michiels C
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01359-9
Subject(s) - aryl hydrocarbon receptor nuclear translocator , hsp90 , aryl hydrocarbon receptor , transcription factor , geldanamycin , pas domain , hypoxia inducible factor 1 , microbiology and biotechnology , fusion protein , heat shock protein , regulator , chaperone (clinical) , chemistry , transcription (linguistics) , biology , biochemistry , gene , recombinant dna , medicine , linguistics , philosophy , pathology
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.