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Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway

Author

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  • Jianshuang Li

    (Van Andel Research Institute
    Wuhan University)

  • Di Lu

    (Van Andel Research Institute)

  • Hong Dou

    (University of Missouri)

  • Huadie Liu

    (Van Andel Research Institute
    Central South University)

  • Kevin Weaver

    (Van Andel Research Institute)

  • Wenjun Wang

    (Wuhan University)

  • Jiada Li

    (Central South University)

  • Edward T.H. Yeh

    (University of Missouri)

  • Bart O. Williams

    (Van Andel Research Institute)

  • Ling Zheng

    (Wuhan University)

  • Tao Yang

    (Van Andel Research Institute)

Abstract

The development, growth, and renewal of skeletal tissues rely on the function of osteochondroprogenitors (OCPs). Protein sumoylation/desumoylation has emerged as a pivotal mechanism for stem cell/progenitor homeostasis, and excessive sumoylation has been associated with cell senescence and tissue aging, but its role in regulating OCP function is unclear. Here we show that postnatal loss of the desumoylase SUMO1/sentrin-specific peptidase 6 (SENP6) causes premature aging. OCP-specific SENP6 knockout mice exhibit smaller skeletons, with elevated apoptosis and cell senescence in OCPs and chondrocytes. In Senp6 ‒/‒ cells, the two most significantly elevated pathways are p53 signaling and senescence-associated secreted phenotypes (SASP), and Trp53 loss partially rescues the skeletal and cellular phenotypes caused by Senp6 loss. Furthermore, SENP6 interacts with, desumoylates, and stabilizes TRIM28, suppressing p53 activity. Our data reveals a crucial role of the SENP6–p53 axis in maintaining OCP homeostasis during skeletal development.

Suggested Citation

  • Jianshuang Li & Di Lu & Hong Dou & Huadie Liu & Kevin Weaver & Wenjun Wang & Jiada Li & Edward T.H. Yeh & Bart O. Williams & Ling Zheng & Tao Yang, 2018. "Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02413-3
    DOI: 10.1038/s41467-017-02413-3
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    Cited by:

    1. Joana S. Rodrigues & Miguel Chenlo & Susana B. Bravo & Sihara Perez-Romero & Maria Suarez-Fariña & Tomas Sobrino & Rebeca Sanz-Pamplona & Román González-Prieto & Manuel Narciso Blanco Freire & Ruben N, 2024. "dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe," Nature Communications, Nature, vol. 15(1), pages 1-30, December.
    2. Sarah Tessier & Omar Ferhi & Marie-Claude Geoffroy & Román González-Prieto & Antoine Canat & Samuel Quentin & Marika Pla & Michiko Niwa-Kawakita & Pierre Bercier & Domitille Rérolle & Marilyn Tirard &, 2022. "Exploration of nuclear body-enhanced sumoylation reveals that PML represses 2-cell features of embryonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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