Ubiquitin precursor with C-terminal extension promotes proteostasis and longevity
Year: 2025
Type: article
Abstract: Ubiquitin is a conserved modifier regulating the stability and function of numerous target proteins. In all eukaryotes, polyubiquitin precursors are generated and processed into ubiquitin monomers. The final ubiquitin unit always contains a C-terminal extension, but its physiological significance is unknown. Here, we show that C-terminally extended ubiquitin, termed CxUb, is essential for stress resistance, mitophagy, and longevity in Saccharomyces cerevisiae and Caenorhabditis elegans. CxUb forms ubiquitin chains and binds to a previously undescribed region within the ubiquitin chain-elongating E4 enzyme Ufd2, which also functions during stress and aging. Ufd2 recognizes CxUb and conjugates it to substrate proteins, triggering their degradation. By contrast, CxUb is not required for basal housekeeping functions of the ubiquitin-proteasome system. These data suggest that the CxUb encodes a functionally unique ubiquitin form, specialized for proteostasis defects, expanding the code of post-translational modification processes.
Source: Molecular Cell
Authors: Selver Altin, Tânia Simões, Christina Behrendt, Vincent Anton, Dennis Domke, Kai Mayor Völtzke, Rajesh Kumar, Hendrik Nolte, Thomas Hermanns, Nahal Brocke-Ahmadinejad, Katja Bendrin, Marcel Zimmermann, Reinhard Büttner, Natascia Ventura, Marcus Krüger, R. Jürgen Dohmen, Kay Hofmann, Thorsten Hoppe, Andreas S. Reichert, Mafalda Escobar-Henriques
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Awards: G1046235988, SFB 1535: Mikrobielle Netzwerke – von Organellen bis hin zu Reichübergreifenden Lebensgemeinschaften, G1471829834, G1792559332, EXC 2030: CECAD Exzellent in Alternsforschung, G3308698521, G3558778216, G4234442455, G4885339532, G541305665, G5744689038, SFB 1218: Regulation der zellulären Funktion durch Mitochondrien, G6175506856
OpenAlex ID: W4414532942