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YAP promotes the activation of NLRP3 inflammasome via blocking K27-linked polyubiquitination of NLRP3

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Listed:
  • Dan Wang

    (Central South University
    Central South University)

  • Yening Zhang

    (Central South University)

  • Xueming Xu

    (Central South University)

  • Jianfeng Wu

    (Xiamen University)

  • Yue Peng

    (Central South University)

  • Jing Li

    (Central South University)

  • Ruiheng Luo

    (Central South University)

  • Lingmin Huang

    (Central South University)

  • Liping Liu

    (Central South University)

  • Songlin Yu

    (Central South University
    Central South University)

  • Ningjie Zhang

    (Central South University)

  • Ben Lu

    (Central South University
    Central South University
    Central South University)

  • Kai Zhao

    (Central South University)

Abstract

The transcription coactivator YAP plays a vital role in Hippo pathway for organ-size control and tissue homeostasis. Recent studies have demonstrated YAP is closely related to immune disorders and inflammatory diseases, but the underlying mechanisms remain less defined. Here, we find that YAP promotes the activation of NLRP3 inflammasome, an intracellular multi-protein complex that orchestrates host immune responses to infections or sterile injuries. YAP deficiency in myeloid cells significantly attenuates LPS-induced systemic inflammation and monosodium urate (MSU) crystals-induced peritonitis. Mechanistically, YAP physically interacts with NLRP3 and maintains the stability of NLRP3 through blocking the association between NLRP3 and the E3 ligase β-TrCP1, the latter increases the proteasomal degradation of NLRP3 via K27-linked ubiquitination at lys380. Together, these findings establish a role of YAP in the activation of NLRP3 inflammasome, and provide potential therapeutic target to treat the NLRP3 inflammasome-related diseases.

Suggested Citation

  • Dan Wang & Yening Zhang & Xueming Xu & Jianfeng Wu & Yue Peng & Jing Li & Ruiheng Luo & Lingmin Huang & Liping Liu & Songlin Yu & Ningjie Zhang & Ben Lu & Kai Zhao, 2021. "YAP promotes the activation of NLRP3 inflammasome via blocking K27-linked polyubiquitination of NLRP3," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22987-3
    DOI: 10.1038/s41467-021-22987-3
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    Cited by:

    1. Vishwas Mishra & Anna Crespo-Puig & Callum McCarthy & Tereza Masonou & Izabela Glegola-Madejska & Alice Dejoux & Gabriella Dow & Matthew J. G. Eldridge & Luciano H. Marinelli & Meihan Meng & Shijie Wa, 2023. "IL-1β turnover by the UBE2L3 ubiquitin conjugating enzyme and HECT E3 ligases limits inflammation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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