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

Jun Yang, Yoshinori Takahashi, Erdong Cheng, Jihong Liu, Paul F. Terranova, Bin Zhao, J. Brantley Thrasher, Hong-Gang Wang, Benyi Li

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)861-870
Number of pages10
JournalJournal of Cell Science
Volume123
Issue number6
DOIs
StatePublished - Mar 15 2010

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Autophagy
Cell Survival
Cell Death
Starvation
Serum
Glycogen Synthase Kinase 3 beta
Prostatic Neoplasms
Necrosis
Biomarkers

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Yang, Jun ; Takahashi, Yoshinori ; Cheng, Erdong ; Liu, Jihong ; Terranova, Paul F. ; Zhao, Bin ; Thrasher, J. Brantley ; Wang, Hong-Gang ; Li, Benyi. / GSK-3β promotes cell survival by modulating Bif-1-dependent autophagy and cell death. In: Journal of Cell Science. 2010 ; Vol. 123, No. 6. pp. 861-870.
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Yang, J, Takahashi, Y, Cheng, E, Liu, J, Terranova, PF, Zhao, B, Thrasher, JB, Wang, H-G & Li, B 2010, 'GSK-3β promotes cell survival by modulating Bif-1-dependent autophagy and cell death', Journal of Cell Science, vol. 123, no. 6, pp. 861-870. https://doi.org/10.1242/jcs.060475

GSK-3β promotes cell survival by modulating Bif-1-dependent autophagy and cell death. / Yang, Jun; Takahashi, Yoshinori; Cheng, Erdong; Liu, Jihong; Terranova, Paul F.; Zhao, Bin; Thrasher, J. Brantley; Wang, Hong-Gang; Li, Benyi.

In: Journal of Cell Science, Vol. 123, No. 6, 15.03.2010, p. 861-870.

Research output: Contribution to journalArticle

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AU - Li, Benyi

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