TY - JOUR
T1 - Hypoxia-induced activation of HIF-1: Role of HIF-1α-Hsp90 interaction
AU - Minet, Emmanuel
AU - Mottet, Denis
AU - Michel, Gaetan
AU - Roland, Isabelle
AU - Raes, Martine
AU - Remacle, José
AU - Michiels, Carine
PY - 1999/10/29
Y1 - 1999/10/29
N2 - 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.
AB - 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.
KW - Heat shock protein 90
KW - Hypoxia
KW - Hypoxia-inducible factor
UR - http://www.scopus.com/inward/record.url?scp=0032749463&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(99)01359-9
DO - 10.1016/S0014-5793(99)01359-9
M3 - Article
C2 - 10544245
SN - 0014-5793
VL - 460
SP - 251
EP - 256
JO - FEBS Letters
JF - FEBS Letters
IS - 2
ER -