Heat shock protein 90 regulates the stability of MEKK3 in HEK293 cells

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• 作者：Shuping Fang ; Jin Fu ; Xia Yuan ; Cui Han ; Lijun Shi ; Yinqiang Xin ; Lan Luo ; Zhimin Yin
• 关键词：Hsp90 ; MEKK3 ; Geldanamycin ; MG-132 ; HEK293 cells
• 刊名：Cellular Immunology
• 出版年：2009
• 出版时间：2009
• 年：2009
• 卷：259
• 期：1
• 页码：49-55
• 全文大小：893 K

文摘

Heat shock protein 90 (Hsp90) is a molecular chaperone required for the conformational maturation and function of certain signaling proteins. Hsp90 inhibitors cause the inactivation, destabilization and eventual degradation of Hsp90 client proteins through occupying the ATP/ADP binding pocket of Hsp90. In the present study, we found that Hsp90 interacted with MEKK3 in HEK293 cells. Hsp90 inhibitors reduced the level of endogenous MEKK3 in time- and dose-dependent manners, and this decrease was reversed by Hsp90 overexpression. In addition, Hsp90 RNAi destabilized MEKK3. A selective inhibitor of Hsp90, geldanamycin (GA), shortened MEKK3 half-life, and induced ubiquitination and proteasomal degradation of MEKK3. These results strongly suggested that Hsp90 could work as the molecular chaperone of MEKK3.