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Cytoplasmic Daxx Drives Sqstm1/P62 Phase Condensation To Activate Nrf2-Mediated Stress Response., 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 Lu, Shouqing Luo

Department of Microbiology and Immunology Faculty Papers

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 …