Threonine 32 (Thr32) of FoxO3 is critical for TGF-β-induced apoptosis via Bim in hepatocarcinoma cells

• DOI: 10.1007/s13238-014-0121-5
• Publication Date: 2014-12-10T06:51:46Z
• Authors: Xiangxuan Zhao; Yong Liu; Lei Du; Leya He; Biyun Ni; Junbo Hu; Dahai Zhu; Quan Chen
• Keywords: FOXO3; Smad2 Protein

Transforming growth factor-β (TGF-β) exerts apoptotic effects on various types of malignant cells, including liver cancer cells. However, the precise mechanisms by which TGF-β induces apoptosis remain poorly known. In present study, we have showed that threonine 32 (Thr32) residue FoxO3 is critical for to induce via Bim in hepatocarcinoma Hep3B Our data demonstrated induced activation through specific de-phosphorylation at Thr32. TGF-β-activated cooperated with Smad2/3 mediate up-regulation and apoptosis. (de)phosphorylation Thr32 was regulated casein kinase I-ε (CKI-ε). CKI inhibition small molecule D4476 could abrogate TGF-β-induced FoxO/Smad activation, reverse up-regulation, block sequential More importantly, deregulated levels CKI-ε p32FoxO3 were found human tissues. Taken together, our findings suggest there might be a CKI-FoxO/Smad-Bim engine pivotal apoptosis, making it potential therapeutic target treatment.