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Phosphorylation of caspases by a bacterial kinase inhibits host programmed cell death

Author

Listed:
  • Jinli Ge

    (Jilin University)

  • Ying Wang

    (Peking University Health Science Center
    Peking University)

  • Xueyu Li

    (Jilin University)

  • Qian Lu

    (Jilin University)

  • Hangqian Yu

    (Jilin University)

  • Hongtao Liu

    (Jilin University)

  • Kelong Ma

    (Jilin University)

  • Xuming Deng

    (Jilin University)

  • Zhao-Qing Luo

    (Purdue University)

  • Xiaoyun Liu

    (Peking University Health Science Center
    Peking University)

  • Jiazhang Qiu

    (Jilin University)

Abstract

The intracellular bacterial pathogen Legionella pneumophila utilizes the Dot/Icm system to translocate over 330 effectors into the host cytosol. These virulence factors modify a variety of cell processes, including pathways involved in cell death and survival, to promote bacterial proliferation. Here, we show that the effector LegK3 is a eukaryotic-like Ser/Thr kinase that functions to suppress host apoptosis. Mechanistically, LegK3 directly phosphorylates multiple caspases involved in apoptosis signaling, including Caspase-3, Caspase-7, and Caspase-9. LegK3-induced phosphorylation of these caspases occurs at serine (Ser29 in Caspase-3 and Ser199 in Caspase-7) or threonine (Thr102 in Caspase-9) residues located in the prodomain or interdomain linkers. These modifications interfere with the suitability of the caspases as the substrates of initiator caspases or upstream regulators without impacting their proteolytic activity. Collectively, our study reveals a novel strategy used by L. pneumophila to maintain the integrity of infected cells for its intracellular growth.

Suggested Citation

  • Jinli Ge & Ying Wang & Xueyu Li & Qian Lu & Hangqian Yu & Hongtao Liu & Kelong Ma & Xuming Deng & Zhao-Qing Luo & Xiaoyun Liu & Jiazhang Qiu, 2024. "Phosphorylation of caspases by a bacterial kinase inhibits host programmed cell death," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52817-1
    DOI: 10.1038/s41467-024-52817-1
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    References listed on IDEAS

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