C-terminal extension of ubiquitin promotes proteostasis and longevity
Stability and function of target proteins is governed by ubiquitin proteins that are generated as polyubiquitin precurssors and processed into ubiquitin monomers containing C-terminal extension.
The researchers in this study identified CxUb, a C-terminally extended ubiquitin molecule dedicated to overcoming stress and present in all eukaryotic genomes.
CxUb marks client proteins for efficient degradation by the proteasome, ensuring cellular quality control. Mechanistically, 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.
CxUb is not required for basal housekeeping functions of the ubiquitin-proteasome system and its function is critical specifically in stressed cells, safeguarding healthy ones and contributing to healthy aging.
https://www.cell.com/molecular-cell/fulltext/S1097-2765(25)00737-3
