[HTML][HTML] Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1α-degradative pathway
JS Isaacs, YJ Jung, EG Mimnaugh, A Martinez… - Journal of Biological …, 2002 - ASBMB
HIF-1α is a normally labile proangiogenic transcription factor that is stabilized and activated
in hypoxia. Although the von Hippel Lindau (VHL) gene product, the ubiquitin ligase
responsible for regulating HIF-1α protein levels, efficiently targets HIF-1α for rapid
proteasome-dependent degradation under normoxia, HIF-1α is resistant to the destabilizing
effects of VHL under hypoxia. HIF-1α also associates with the molecular chaperone Hsp90.
To examine the role of Hsp90 in HIF-1α function, we used renal carcinoma cell (RCC) lines …
in hypoxia. Although the von Hippel Lindau (VHL) gene product, the ubiquitin ligase
responsible for regulating HIF-1α protein levels, efficiently targets HIF-1α for rapid
proteasome-dependent degradation under normoxia, HIF-1α is resistant to the destabilizing
effects of VHL under hypoxia. HIF-1α also associates with the molecular chaperone Hsp90.
To examine the role of Hsp90 in HIF-1α function, we used renal carcinoma cell (RCC) lines …