XBP-1u suppresses autophagy by promoting the degradation of FoxO1 in cancer cells |
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| Authors: | Ying Zhao Xue Li Mu-Yan Cai Ke Ma Jing Yang Jingyi Zhou Wan Fu Fu-Zheng Wei Lina Wang Dan Xie Wei-Guo Zhu |
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| Affiliation: | 1.Key Laboratory of Carcinogenesis and Translational Research of Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China;2.State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, China;2.Peking-Tsinghua University Center for Life Sciences, Peking University, Beijing 100871, China |
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| Abstract: | ![]()
Autophagy is activated to maintain cellular energy homeostasis in response to nutrient starvation. However, autophagy is not persistently activated, which is poorly understood at a mechanistic level. Here, we report that turnover of FoxO1 is involved in the dynamic autophagic process caused by glutamine starvation. X-box-binding protein-1u (XBP-1u) has a critical role in FoxO1 degradation by recruiting FoxO1 to the 20S proteasome. In addition, the phosphorylation of XBP-1u by extracellular regulated protein kinases1/2 (ERK1/2) on Ser61 and Ser176 was found to be critical for the increased interaction between XBP-1u and FoxO1 upon glutamine starvation. Furthermore, knockdown of XBP-1u caused the sustained level of FoxO1 and the persistent activation of autophagy, leading to a significant decrease in cell viability. Finally, the inverse correlation between XBP-1u and FoxO1 expression agrees well with the expression profiles observed in many human cancer tissues. Thus, our findings link the dynamic process of autophagy to XBP-1u-induced FoxO1 degradation. |
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| Keywords: | FoxO1 XBP-1u ERK autophagy cancer |
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