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Innate immune and proinflammatory signals activate the Hippo pathway via a Tak1-STRIPAK-Tao axis

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  • Yinan Yang

    (Xiamen University)

  • Huijing Zhou

    (Xiamen University)

  • Xiawei Huang

    (Xiamen University)

  • Chengfang Wu

    (Xiamen University)

  • Kewei Zheng

    (Xiamen University)

  • Jingrong Deng

    (Xiamen University)

  • Yonggang Zheng

    (University of Texas Southwestern Medical Center)

  • Jiahui Wang

    (Xiamen University)

  • Xiaofeng Chi

    (Xiamen University)

  • Xianjue Ma

    (Westlake Laboratory of Life Sciences and Biomedicine)

  • Huimin Pan

    (Xiamen University)

  • Rui Shen

    (Xiamen University)

  • Duojia Pan

    (University of Texas Southwestern Medical Center)

  • Bo Liu

    (Xiamen University)

Abstract

The Hippo pathway controls developmental, homeostatic and regenerative tissue growth, and is frequently dysregulated in various diseases. Although this pathway can be activated by innate immune/inflammatory stimuli, the underlying mechanism is not fully understood. Here, we identify a conserved signaling cascade that leads to Hippo pathway activation by innate immune/inflammatory signals. We show that Tak1, a key kinase in innate immune/inflammatory signaling, activates the Hippo pathway by inducing the lysosomal degradation of Cka, an essential subunit of the STRIPAK PP2A complex that suppresses Hippo signaling. Suppression of STRIPAK results in the activation of Hippo pathway through Tao-Hpo signaling. We further show that Tak1-mediated Hippo signaling is involved in processes ranging from cell death to phagocytosis and innate immune memory. Our findings thus reveal a molecular connection between innate immune/inflammatory signaling and the evolutionally conserved Hippo pathway, thus contributing to our understanding of infectious, inflammatory and malignant diseases.

Suggested Citation

  • Yinan Yang & Huijing Zhou & Xiawei Huang & Chengfang Wu & Kewei Zheng & Jingrong Deng & Yonggang Zheng & Jiahui Wang & Xiaofeng Chi & Xianjue Ma & Huimin Pan & Rui Shen & Duojia Pan & Bo Liu, 2024. "Innate immune and proinflammatory signals activate the Hippo pathway via a Tak1-STRIPAK-Tao axis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44542-y
    DOI: 10.1038/s41467-023-44542-y
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