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Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response

Author

Listed:
  • Yi Yang

    (University of Plymouth)

  • Thea L. Willis

    (University of Plymouth)

  • Robert W. Button

    (University of Plymouth)

  • Conor J. Strang

    (University of Plymouth)

  • Yuhua Fu

    (Fudan University)

  • Xue Wen

    (Fudan University)

  • Portia R. C. Grayson

    (University of Plymouth)

  • Tracey Evans

    (University of Plymouth)

  • Rebecca J. Sipthorpe

    (University of Plymouth)

  • Sheridan L. Roberts

    (University of Plymouth)

  • Bing Hu

    (University of Plymouth)

  • Jianke Zhang

    (Thomas Jefferson University)

  • Boxun Lu

    (Fudan University)

  • Shouqing Luo

    (University of Plymouth)

Abstract

Autophagy cargo recognition and clearance are essential for intracellular protein quality control. SQSTM1/p62 sequesters intracellular aberrant proteins and mediates cargo delivery for their selective autophagic degradation. The formation of p62 non-membrane-bound liquid compartments is critical for its function as a cargo receptor. The regulation of p62 phase separation/condensation has yet been poorly characterised. Using an unbiased yeast two-hybrid screening and complementary approaches, we found that DAXX physically interacts with p62. Cytoplasmic DAXX promotes p62 puncta formation. We further elucidate that DAXX drives p62 liquid phase condensation by inducing p62 oligomerisation. This effect promotes p62 recruitment of Keap1 and subsequent Nrf2-mediated stress response. The present study suggests a mechanism of p62 phase condensation by a protein interaction, and indicates that DAXX regulates redox homoeostasis, providing a mechanistic insight into the prosurvival function of DAXX.

Suggested Citation

  • Yi Yang & Thea L. Willis & Robert W. Button & Conor J. Strang & Yuhua Fu & Xue Wen & Portia R. C. Grayson & Tracey Evans & Rebecca J. Sipthorpe & Sheridan L. Roberts & Bing Hu & Jianke Zhang & Boxun L, 2019. "Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11671-2
    DOI: 10.1038/s41467-019-11671-2
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    Cited by:

    1. Cezanne Miete & Gonzalo P. Solis & Alexey Koval & Martina Brückner & Vladimir L. Katanaev & Jürgen Behrens & Dominic B. Bernkopf, 2022. "Gαi2-induced conductin/axin2 condensates inhibit Wnt/β-catenin signaling and suppress cancer growth," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Iqbal Mahmud & Guimei Tian & Jia Wang & Tarun E. Hutchinson & Brandon J. Kim & Nikee Awasthee & Seth Hale & Chengcheng Meng & Allison Moore & Liming Zhao & Jessica E. Lewis & Aaron Waddell & Shangtao , 2023. "DAXX drives de novo lipogenesis and contributes to tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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