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Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth

Author

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  • Ting Sun

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University
    The First Affiliated Hospital of Zhengzhou University)

  • Xuan Li

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Peng Zhang

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Wen-Dan Chen

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Hai-liang Zhang

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Dan-Dan Li

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Rong Deng

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Xiao-Jun Qian

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Lin Jiao

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Jiao Ji

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Yun-Tian Li

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Rui-Yan Wu

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Yan Yu

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Gong-Kan Feng

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

  • Xiao-Feng Zhu

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University)

Abstract

Beclin 1, a protein essential for autophagy, regulates autophagy by interacting with Vps34 and other cofactors to form the Beclin 1 complex. Modifications of Beclin 1 may lead to the induction, inhibition or fine-tuning of the autophagic response under a variety of conditions. Here we show that Beclin 1 is acetylated by p300 and deacetylated by SIRT1 at lysine residues 430 and 437. In addition, the phosphorylation of Beclin 1 at S409 by CK1 is required for the subsequent p300 binding and Beclin 1 acetylation. Beclin 1 acetylation inhibits autophagosome maturation and endocytic trafficking by promoting the recruitment of Rubicon. In tumour xenografts, the expression of 2KR mutant Beclin 1 (substitution of K430 and K437 to arginines) leads to enhanced autophagosome maturation and tumour growth suppression. Therefore, our study identifies an acetylation-dependent regulatory mechanism governing Beclin 1 function in autophagosome maturation and tumour growth.

Suggested Citation

  • Ting Sun & Xuan Li & Peng Zhang & Wen-Dan Chen & Hai-liang Zhang & Dan-Dan Li & Rong Deng & Xiao-Jun Qian & Lin Jiao & Jiao Ji & Yun-Tian Li & Rui-Yan Wu & Yan Yu & Gong-Kan Feng & Xiao-Feng Zhu, 2015. "Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8215
    DOI: 10.1038/ncomms8215
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    Cited by:

    1. Juan Li & Yang Wang & Yue Luo & Yang Liu & Yong Yi & Jinsong Li & Yang Pan & Weiyuxin Li & Wanbang You & Qingyong Hu & Zhiqiang Zhao & Yujun Zhang & Yang Cao & Lingqiang Zhang & Junying Yuan & Zhi-Xio, 2022. "USP5-Beclin 1 axis overrides p53-dependent senescence and drives Kras-induced tumorigenicity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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