Figure 6.

Simvastatin (Sim) diminishes the chaperone activity of K292‐acetylated heat shock protein 90α (Hsp90α). Sim abrogated the complex formation of K292‐acetylated Hsp90 with Hsp90 cochaperones in MDA‐MB‐231 (A) and MDA‐MB‐468 (B) cells treated as indicated for 12 hours. Cell lysates were immunoprecipitated (IP) using acK292 antibody followed by immunoblotting (IB) with the indicated antibodies. Similarly, Sim abrogated the complex formation of K292‐acetylated Hsp90α with protein kinase clients in MDA‐MB‐231 (C) and MDA‐MB‐468 cells (D). E, Expression of Hsp90 clients regulated by combined treatment with Sim and LBH589 (LBH) is independent of the mevalonate (MEV) pathway. CDK, cyclin‐dependent kinase; Ctl, control; HOP, Hsp70‐Hsp90 organizing protein 1; HSF1, Heat shock factor 1; p‐HSF1, S326 phosphorylated Heat shock factor 1; TGFβR2, TGF‐β receptor type 2