CaMKII-mediated Beclin 1 phosphorylation regulates autophagy that promotes degradation of Id and neuroblastoma cell differentiation

Xuan Li, Xiao-Qi Wu, Rong Deng, Dan-Dan Li, Jun Tang, Wen-Dan Chen, Jing-Hong Chen, Jiao Ji, Lin Jiao, Shan Jiang, Fen Yang, Gong-Kan Feng, Ravichandran Senthilkumar, Fei Yue, Hai-Liang Zhang, Rui-Yan Wu, Yan Yu, Xue-Lian Xu, Jia Mai, Zhi-Ling Li, Xiao-Dan Peng, Yun Huang, Xiang Huang, Ning-Fang Ma, Qian Tao, Yi-Xin Zeng and Xiao-Feng Zhu ()
Additional contact information
Xuan Li: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Xiao-Qi Wu: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Rong Deng: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Dan-Dan Li: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Jun Tang: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Wen-Dan Chen: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Jing-Hong Chen: The Second Affiliated Hospital, Guangzhou Medical University
Jiao Ji: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Lin Jiao: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Shan Jiang: The First Affiliated Hospital, Chongqing Medical University
Fen Yang: Nanjing Medical University
Gong-Kan Feng: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Ravichandran Senthilkumar: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Fei Yue: Texas A&M University Health Science Center
Hai-Liang Zhang: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Rui-Yan Wu: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Yan Yu: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Xue-Lian Xu: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Jia Mai: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Zhi-Ling Li: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Xiao-Dan Peng: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Yun Huang: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Xiang Huang: Jinan University
Ning-Fang Ma: School of Basic Medical Sciences, Affiliated Cancer Hospital and Institute of Guangzhou Medical University
Qian Tao: Prince of Wales Hospital, The Chinese University of Hong Kong
Yi-Xin Zeng: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
Xiao-Feng Zhu: Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: Abstract Autophagy is a degradative pathway that delivers cellular components to the lysosome for degradation. The role of autophagy in cell differentiation is poorly understood. Here we show that CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. Meanwhile, CaMKII can also promote K63-linked ubiquitination of inhibitor of differentiation 1/2 (Id-1/2) by catalyzing phosphorylation of Id proteins and recruiting TRAF-6. Ubiquitinated Id-1/Id-2 can then bind to p62 and be transported to autolysosomes for degradation. Id degradation promotes the differentiation of neuroblastoma cells and reduces the proportion of stem-like cells. Our study proposes a mechanism by which autophagic degradation of Id proteins can regulate cell differentiation. This suggests that targeting of CaMKII and the regulation of autophagic degradation of Id may be an effective therapeutic strategy to induce cell differentiation in neuroblastoma.

Date: 2017
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DOI: 10.1038/s41467-017-01272-2

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