GSK-3β promotes cell survival by modulating Bif-1-dependent autophagy and cell death

• Published in: Journal of cell science Vol. 123; no. 6; pp. 861 - 870
• Main Authors: Yang, Jun, Takahashi, Yoshinori, Cheng, Erdong, Liu, Jihong, Terranova, Paul F, Zhao, Bin, Thrasher, J. Brantley, Wang, Hong-Gang, Li, Benyi
• Format: Journal Article
• Language: English
• Published: The Company of Biologists Limited 15.03.2010; Company of Biologists
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.060475

Glycogen synthase kinase 3 beta (GSK-3β) is constantly active in cells and its activity increases after serum deprivation, indicating that GSK-3β might play a major role in cell survival under serum starvation. In this study, we attempted to determine how GSK-3β promotes cell survival after serum depletion. Under full culture conditions (10% FBS), GSK-3β inhibition with chemical inhibitors or siRNAs failed to induce cell death in human prostate cancer cells. By contrast, under conditions of serum starvation, a profound necrotic cell death was observed as evidenced by cellular morphologic features and biochemical markers. Further analysis revealed that GSK-3β-inhibition-induced cell death was in parallel with an extensive autophagic response. Interestingly, blocking the autophagic response switched GSK-3β-inhibition-induced necrosis to apoptotic cell death. Finally, GSK-3β inhibition resulted in a remarkable elevation of Bif-1 protein levels, and silencing Bif-1 expression abrogated GSK-3β-inhibition-induced autophagic response and cell death. Taken together, our study suggests that GSK-3β promotes cell survival by modulating Bif-1-dependent autophagic response and cell death.