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Study Identifies Stress-Activated Ubiquitin Precursor That Enhances Proteostasis and Longevity

Researchers report a stress-responsive form found across eukaryotes that selectively enhances clearance of damaged proteins.

Overview

  • In Molecular Cell, teams in Cologne and Düsseldorf led by Mafalda Escobar-Henriques and Andreas Reichert describe CxUb, a C‑terminally extended ubiquitin precursor engaged under stress.
  • CxUb was necessary and sufficient to resolve stress, restore proteostasis, and extend lifespan in Saccharomyces cerevisiae and Caenorhabditis elegans.
  • Only CxUb, not standard ubiquitin, amplified tagging of abnormal proteins during stress while leaving housekeeping functions in healthy cells unaffected.
  • The precursor appears to be universally present in eukaryotes and had been largely overlooked as inactive before these experiments.
  • The authors highlight therapeutic potential for cancer and neurodegenerative diseases as a future direction, with validation in mammalian systems planned and work supported by DFG and other funders.