Redefining the Phenotype of Heat Shock Protein 90 (Hsp90) Inhibitors

详细信息    查看全文

• 作者：Dr. Yao Wang ; Yen Chin Koay and Prof. Shelli R. McAlpine
• 刊名：Chemistry - A European Journal
• 出版年：2017
• 出版时间：February 10, 2017
• 年：2017
• 卷：23
• 期：9
• 页码：2010-2013
• 全文大小：687K
• ISSN：1521-3765

文摘

The phenotypes produced when cells are treated with the heat shock protein 90 (Hsp90) inhibitors AUY922 or 17-AAG (classical inhibitors) are different to those produced when cells are knocked down with Hsp90α. Pull-down assays using classical inhibitors suggest that these molecules bind to multiple targets other than Hsp90. Classical inhibitors also induce similar protein markers as other anti-cancer therapies cisplatin and bortezomib that do not target Hsp90. Together these data suggest that AUY922 and 17-AAG acts on multiple targets and likely kills cells through multiple mechanisms. Comparing these classical inhibitors to the effects seen when treating cells with C-terminal Hsp90 modulators reveals that C-terminal modulators effectively bind to Hsp90, and induce phenotypic markers consistent with the Hsp90α CRISPR knockdown data. Our findings challenge the current interpretation of Hsp90 inhibitors and suggest that a large body of literature that describes the Hsp90 phenotype and inhibitors is re-examined in this context.