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USP8 maintains embryonic stem cell stemness via deubiquitination of EPG5

Author

Listed:
  • Haifeng Gu

    (Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xingxing Shi

    (Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Chao Liu

    (Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Chaoqun Wang

    (Institute of Zoology, Chinese Academy of Sciences
    Qufu Normal University)

  • Ning Sui

    (Institute of Zoology, Chinese Academy of Sciences
    Qufu Normal University)

  • Yu Zhao

    (Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jiaqi Gong

    (Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Fuping Wang

    (Institute of Zoology, Chinese Academy of Sciences
    Hebei University)

  • Hong Zhang

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Wei Li

    (Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Tongbiao Zhao

    (Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Embryonic stem cells (ESCs) can propagate in an undifferentiated state indefinitely in culture and retain the potential to differentiate into any somatic lineage as well as germ cells. The catabolic process autophagy has been reported to be involved in ESC identity regulation, but the underlying mechanism is still largely unknown. Here we show that EPG5, a eukaryotic-specific autophagy regulator which mediates autophagosome/lysosome fusion, is highly expressed in ESCs and contributes to ESC identity maintenance. We identify that the deubiquitinating enzyme USP8 binds to the Coiled-coil domain of EPG5. Mechanistically, USP8 directly removes non-classical K63-linked ubiquitin chains from EPG5 at Lysine 252, leading to enhanced interaction between EPG5 and LC3. We propose that deubiquitination of EPG5 by USP8 guards the autophagic flux in ESCs to maintain their stemness. This work uncovers a novel crosstalk pathway between ubiquitination and autophagy through USP8-EPG5 interaction to regulate the stemness of ESCs.

Suggested Citation

  • Haifeng Gu & Xingxing Shi & Chao Liu & Chaoqun Wang & Ning Sui & Yu Zhao & Jiaqi Gong & Fuping Wang & Hong Zhang & Wei Li & Tongbiao Zhao, 2019. "USP8 maintains embryonic stem cell stemness via deubiquitination of EPG5," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09430-4
    DOI: 10.1038/s41467-019-09430-4
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    Cited by:

    1. Shaoyu Wang & Kui Li & Hui Gao & Zepeng Liu & Shuang Shi & Qiang Tan & Zhengguang Wang, 2021. "Ubiquitin-specific peptidase 8 regulates proliferation and early differentiation of sheep skeletal muscle satellite cells," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 66(3), pages 87-96.
    2. Wenjun Xiong & Xueliang Gao & Tiantian Zhang & Baishan Jiang & Ming-Ming Hu & Xia Bu & Yang Gao & Lin-Zhou Zhang & Bo-Lin Xiao & Chuan He & Yishuang Sun & Haiou Li & Jie Shi & Xiangling Xiao & Bolin X, 2022. "USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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