Ubiquitin-Proteasome Pathway (UPP)

The Ubiquitin-Proteasome Pathway (UPP) is a highly conserved, primary cytosolic proteolytic machinery responsible for the targeted degradation of various damaged, misfolded, or short-lived regulatory proteins in eukaryotic cells. It consists of two main components: the ubiquitination system (E1, E2, E3 enzymes) that tags target proteins with polyubiquitin chains, and the 26S proteasome complex that then degrades these tagged proteins into smaller peptides. The UPP is crucial for protein quality control, cell cycle regulation, immune response, and apoptosis. Dysregulation of the UPP is implicated in numerous diseases, including cancer and neurodegenerative disorders, making it a significant therapeutic target.

Other names

Ubiquitin-Proteasome System

Therapeutic targeting of the UPP involves inhibiting its components, such as the proteasome (e.g., bortezomib), deubiquitinating enzymes (DUBs), or modulating E3 ligases, to either prevent protein breakdown or selectively target specific proteins for degradation.