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In contrast, downregulation of Hsp90β had little effect on hypoxia-induced accumulation of HIF-1α. Instead, Hsp90β protects signaling molecules responsible for cellular homeostasis from assault by 17-AAG (17-N-allylamino-17-demethoxygeldanamycin), a general ATPase inhibitor of both Hsp90α and Hsp90β. Since targeting Hsp90β gene is lethal in both cultured cells and in mice, our new finding explains the toxicity of the previous inhibitor trials and identifies the specific binding of Hsp90α to HIF-1α as a new therapeutic window for deve

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