FIGURE 6.

Cdc37 modulates Hsp90 inhibitor efficacy for tau. A, M17 cells were transfected with Cdc37 siRNA for 48 h and then treated with the Hsp90 inhibitor 17-AAG for 24 h. Lysates were analyzed by Western blotting. The quantification plot suggests that Cdc37 knockdown dramatically increased the efficacy of the 17-AAG drug for endogenous tau reduction. pTau, phospho-tau. B, HeLa cells stably expressing V5-tagged tau (HeLaC3) were transfected with Cdc37 siRNA and treated with 17-AAG as indicated. The quantification plot shows that Cdc37 knockdown (gray bars) increased the efficacy of the 17-AAG drug in a dose-dependent manner compared with cells transfected with control siRNA (black bars). C, HeLaC3 cells were transfected with the Cdc37 plasmid for 24 h and then treated with 17-AAG for 24 h. The quantification plot shows that Cdc37 overexpression (OE) prevented tau from 17-AAG-mediated degradation. Tau immunoreactivity was assessed with antibody PHF-1. Error bars indicate S.D., and percent values were calculated as a percent of the loading control (actin or GAPDH) or as a percent of cells transfected under control (Ctrl) conditions following normalization to the loading control.