HSP27 modulates survival signaling networks in cells treated with curcumin and TRAIL

Abstract

The combination of curcumin and TRAIL and their role in enhancing apoptotic cell death has been reported by many studies. However, the exact molecular mechanism of apoptosis mediated by curcumin and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is not yet completely understood. In this study, we observed a close connection between dephosphorylated Akt and an increase in phosphorylated heat shock protein 27 (HSP27) during combined treatment with curcumin and TRAIL. Akt dephosphorylation was cumulatively regulated by protein phosphatase 1 (PP1), phosphoinositide-dependent kinase-1 (PDK1), and src. PP1 and PDK1 directly interacted with HSP27, whereas src indirectly interacted with HSP27 via the tumor necrosis factor receptor-associated factor 6 complex. In conclusion, HSP27 modulated cell survival by its interactions with various binding partners, depending on the level of phosphorylated HSP27.