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Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation

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  • Chun-Ping Cui

    (Beijing Institute of Lifeomics)

  • Yuan Zhang

    (Beijing Institute of Lifeomics)

  • Chanjuan Wang

    (Beijing Institute of Lifeomics)

  • Fang Yuan

    (Nanjing Medical University
    Chinese Academy of Science)

  • Hongchang Li

    (Beijing Institute of Lifeomics)

  • Yuying Yao

    (Beijing Institute of Lifeomics)

  • Yuhan Chen

    (Beijing Institute of Lifeomics)

  • Chunnan Li

    (Beijing Institute of Lifeomics)

  • Wenyi Wei

    (Harvard Medical School)

  • Cui Hua Liu

    (Chinese Academy of Sciences)

  • Fuchu He

    (Beijing Institute of Lifeomics)

  • Yan Liu

    (Nanjing Medical University
    Chinese Academy of Science)

  • Lingqiang Zhang

    (Beijing Institute of Lifeomics)

Abstract

Sox2 is a key transcriptional factor for maintaining pluripotency of stem cells. Sox2 deficiency causes neurodegeneration and impairs neurogenesis. Although the transcriptional regulation of Sox2 has been extensively studied, the mechanisms that control Sox2 protein turnover are yet to be clarified. Here we show that the RING-finger ubiquitin ligase complex CUL4ADET1-COP1 and the deubiquitylase OTUD7B govern Sox2 protein stability during neural progenitor cells (NPCs) differentiation. Sox2 expression declines concordantly with OTUD7B and reciprocally with CUL4A and COP1 levels upon NPCs differentiation. COP1, as the substrate receptor, interacts directly with and ubiquitylates Sox2, while OTUD7B removes polyUb conjugates from Sox2 and increases its stability. COP1 knockdown stabilizes Sox2 and prevents differentiation, while OTUD7B knockdown destabilizes Sox2 and induces differentiation. Thus, CUL4ADET1-COP1 and OTUD7B exert opposite roles in regulating Sox2 protein stability at the post-translational level, which represents a critical regulatory mechanism involved in the maintenance and differentiation of NPCs.

Suggested Citation

  • Chun-Ping Cui & Yuan Zhang & Chanjuan Wang & Fang Yuan & Hongchang Li & Yuying Yao & Yuhan Chen & Chunnan Li & Wenyi Wei & Cui Hua Liu & Fuchu He & Yan Liu & Lingqiang Zhang, 2018. "Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07025-z
    DOI: 10.1038/s41467-018-07025-z
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    Cited by:

    1. Tatenda Mahlokozera & Bhuvic Patel & Hao Chen & Patrick Desouza & Xuan Qu & Diane D. Mao & Daniel Hafez & Wei Yang & Rukayat Taiwo & Mounica Paturu & Afshin Salehi & Amit D. Gujar & Gavin P. Dunn & Ni, 2021. "Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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