title: Heat shock protein 90 regulates the stability of MEKK3 in HEK293 cells.
abstract: 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.
authors: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, PR China.
authors: Shuping
authors: S
authors: Fang
authors: Jin
authors: J
authors: Fu
authors: Xia
authors: X
authors: Yuan
authors: Cui
authors: C
authors: Han
authors: Lijun
authors: L
authors: Shi
authors: Yinqiang
authors: Y
authors: Xin
authors: Lan
authors: L
authors: Luo
authors: Zhimin
authors: Z
authors: Yin
mesh_terms: D016227:Benzoquinones / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004795:Enzyme Stability; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D048748:MAP Kinase Kinase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D034622:RNA Interference; D014162:Transfection
chemical_list: D016227:Benzoquinones; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D048748:MAP Kinase Kinase Kinase 3; C482625:MAP3K3 protein, human; D046988:Proteasome Endopeptidase Complex; C001277:geldanamycin