机构：[1]State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, 510060 Guangzhou, China.其他部门华南肿瘤学国家重点实验室中山大学肿瘤防治中心[2]The 3rd Affiliated Hospital, Sun Yat-sen University, 510620 Guangzhou, China.[3]Department of Hematology, The Second Affiliated Hospital, Guangzhou Medical University, 510260 Guangzhou, China.[4]Department of Oncology, The First Affiliated Hospital, Chongqing Medical University, 400016 Chongqing, China.内科系统肿瘤科（放疗治疗室）重庆医科大学附属第一医院[5]Department of Biochemistry and Molecular Biology, Nanjing Medical University, 211166 Nanjing, China.[6]Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA.[7]The School of Medicine, Jinan University, 510632 Guangzhou, China.[8]Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 511436 Guangzhou, China.[9]Sir YK Pao Cancer Centre, Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
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 K63linked 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.
基金：
National Natural Science Foundation of China [81630079, 81572605, 81572732, 81772835, 81572493]; Science and Technology Project of Guangdong Province [2014B050504004, 2015B050501005]; Natural Science Foundation of Guangdong Province [2014A030313010, 2014A030313017]; Science and Technology Project of Guangzhou [201504010038, 201707010086]; Fundamental Research Funds for the Central Universities [17ykjc25]; Pearl River Nova Program of Guangzhou [2014J2200039]; Major Science and Technology Project of National Basic Research Program (973 Program) of China [2012CB967004]
语种：
外文
被引次数：
WOS：
中科院(CAS)分区：
出版当年[2017]版：
大类|1 区综合性期刊
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最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, 510060 Guangzhou, China.
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, 510060 Guangzhou, China.
推荐引用方式(GB/T 7714)：
Li Xuan,Wu Xiao-Qi,Deng Rong,et al.CaMKII-mediated Beclin 1 phosphorylation regulates autophagy that promotes degradation of Id and neuroblastoma cell differentiation[J].NATURE COMMUNICATIONS.2017,8(1):-.doi:10.1038/s41467-017-01272-2.
APA：
Li, Xuan,Wu, Xiao-Qi,Deng, Rong,Li, Dan-Dan,Tang, Jun...&Zhu, Xiao-Feng.(2017).CaMKII-mediated Beclin 1 phosphorylation regulates autophagy that promotes degradation of Id and neuroblastoma cell differentiation.NATURE COMMUNICATIONS,8,(1)
MLA：
Li, Xuan,et al."CaMKII-mediated Beclin 1 phosphorylation regulates autophagy that promotes degradation of Id and neuroblastoma cell differentiation".NATURE COMMUNICATIONS 8..1(2017):-
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