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TRIM28 SUMOylates and stabilizes NLRP3 to facilitate inflammasome activation

Author

Listed:
  • Ying Qin

    (Shandong University)

  • Qi Li

    (Shandong University)

  • Wenbo Liang

    (Shandong University)

  • Rongzhen Yan

    (Shandong University)

  • Li Tong

    (Shandong University)

  • Mutian Jia

    (Shandong University)

  • Chunyuan Zhao

    (Shandong University
    Shandong University)

  • Wei Zhao

    (Shandong University)

Abstract

The cellular NLRP3 protein level is crucial for assembly and activation of the NLRP3 inflammasome. Various posttranslational modifications (PTMs), including phosphorylation and ubiquitination, control NLRP3 protein degradation and inflammasome activation; however, the function of small ubiquitin-like modifier (SUMO) modification (called SUMOylation) in controlling NLRP3 stability and subsequent inflammasome activation is unclear. Here, we show that the E3 SUMO ligase tripartite motif-containing protein 28 (TRIM28) is an enhancer of NLRP3 inflammasome activation by facilitating NLRP3 expression. TRIM28 binds NLRP3, promotes SUMO1, SUMO2 and SUMO3 modification of NLRP3, and thereby inhibits NLRP3 ubiquitination and proteasomal degradation. Concordantly, Trim28 deficiency attenuates NLRP3 inflammasome activation both in vitro and in vivo. These data identify a mechanism by which SUMOylation controls the cellular NLRP3 level and inflammasome activation, and reveal correlations and interactions of NLRP3 SUMOylation and ubiquitination during inflammasome activation.

Suggested Citation

  • Ying Qin & Qi Li & Wenbo Liang & Rongzhen Yan & Li Tong & Mutian Jia & Chunyuan Zhao & Wei Zhao, 2021. "TRIM28 SUMOylates and stabilizes NLRP3 to facilitate inflammasome activation," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25033-4
    DOI: 10.1038/s41467-021-25033-4
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    Cited by:

    1. Zhe Gong & Jinjin Zhu & Junxin Chen & Fan Feng & Haitao Zhang & Zheyuan Zhang & Chenxin Song & Kaiyu Liang & Shuhui Yang & Shunwu Fan & Xiangqian Fang & Shuying Shen, 2023. "CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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