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Nat Commun. 2017 Oct 27;8(1):1159. doi: 10.1038/s41467-017-01272-2.

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

Author information

1
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, 510060, Guangzhou, China.
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.
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.
10
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, 510060, Guangzhou, China. zhuxfeng@mail.sysu.edu.cn.

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.

PMID:
29079782
PMCID:
PMC5660092
DOI:
10.1038/s41467-017-01272-2
[Indexed for MEDLINE]
Free PMC Article

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