Heat shock protein 90 regulates the stability of MEKK3 in HEK293 cells.
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.
Mesh Terms:
Benzoquinones, Cell Line, Enzyme Inhibitors, Enzyme Stability, HSP90 Heat-Shock Proteins, Humans, Lactams, Macrocyclic, MAP Kinase Kinase Kinase 3, Proteasome Endopeptidase Complex, RNA Interference, Transfection
Benzoquinones, Cell Line, Enzyme Inhibitors, Enzyme Stability, HSP90 Heat-Shock Proteins, Humans, Lactams, Macrocyclic, MAP Kinase Kinase Kinase 3, Proteasome Endopeptidase Complex, RNA Interference, Transfection
Cell. Immunol.
Date: Jun. 30, 2009
PubMed ID: 19560753
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