%0 Journal Article %A Eunseon Hur %A Hong-Hee Kim %A Su Mi Choi %A Jin Hee Kim %A Sujin Yim %A Ho Jeong Kwon %A Youngyeon Choi %A Dae Kyong Kim %A Mi-Ock Lee %A Hyunsung Park %T Reduction of Hypoxia-Induced Transcription through the Repression of Hypoxia-Inducible Factor-1α/Aryl Hydrocarbon Receptor Nuclear Translocator DNA Binding by the 90-kDa Heat-Shock Protein Inhibitor Radicicol %D 2002 %R 10.1124/mol.62.5.975 %J Molecular Pharmacology %P 975-982 %V 62 %N 5 %X Under low oxygen tension, cells increase the transcription of specific genes involved in angiogenesis, erythropoiesis, and glycolysis. Hypoxia-induced gene expression depends primarily on stabilization of the α subunit of hypoxia-inducible factor-1 (HIF-1α), which acts as a heterodimeric trans-activator with the nuclear protein known as the aryl hydrocarbon receptor nuclear translocator (Arnt). The resulting heterodimer (HIF-1α/Arnt) interacts specifically with the hypoxia-responsive element (HRE), thereby increasing transcription of the genes under HRE control. Our results indicate that the 90-kDa heat-shock protein (Hsp90) inhibitor radicicol reduces the hypoxia-induced expression of both endogenous vascular endothelial growth factor (VEGF) and HRE-driven reporter plasmids. Radicicol treatment (0.5 μg/ml) does not significantly change the stability of the HIF-1α protein and does not inhibit the nuclear localization of HIF-1α. However, this dose of radicicol significantly reduces HRE binding by the HIF-1α/Arnt heterodimer. Our results, the first to show that radicicol specifically inhibits the interaction between the HIF-1α/Arnt heterodimer and HRE, suggest that Hsp90 modulates the conformation of the HIF-1α/Arnt heterodimer, making it suitable for interaction with HRE. Furthermore, we demonstrate that radicicol reduces hypoxia-induced VEGF expression to decrease hypoxia-induced angiogenesis. %U https://molpharm.aspetjournals.org/content/molpharm/62/5/975.full.pdf