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Norway

PMID:38795346  

CUL-6/cullin ubiquitin ligase-mediated degradation of HSP-90 by intestinal lysosomes promotes thermotolerance.

Mario Bardan Sarmiento | Spencer S Gang | Patricija van Oosten-Hawle | Emily R Troemel
Cell reports | 2024

Heat shock can be a lethal stressor. Previously, we described a CUL-6/cullin-ring ubiquitin ligase complex in the nematode Caenorhabditis elegans that is induced by intracellular intestinal infection and proteotoxic stress and that promotes improved survival upon heat shock (thermotolerance). Here, we show that CUL-6 promotes thermotolerance by targeting the heat shock protein HSP-90 for degradation. We show that CUL-6-mediated lowering of HSP-90 protein levels, specifically in the intestine, improves thermotolerance. Furthermore, we show that lysosomal function is required for CUL-6-mediated promotion of thermotolerance and that CUL-6 directs HSP-90 to lysosome-related organelles upon heat shock. Altogether, these results indicate that a CUL-6 ubiquitin ligase promotes organismal survival upon heat shock by promoting HSP-90 degradation in intestinal lysosomes. Thus, HSP-90, a protein commonly associated with protection against heat shock and promoting degradation of other proteins, is itself degraded to protect against heat shock.

Pubmed ID: 38795346

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NIGMS NIH HHS, United States
    Id: K12 GM068524
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM114139
  • Agency: NIA NIH HHS, United States
    Id: R01 AG052622
  • Agency: NIA NIH HHS, United States
    Id: R01 AG082970
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI176639

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