Ubiquitin Proteasome System
Defining New Biology at the Intersection of Mitochondria and UPS
Core Mechanism of UPS
The ubiquitin-proteasome system (UPS) is a fundamental cellular mechanism responsible for the selective degradation of intracellular proteins, playing a critical role in maintaining protein homeostasis, regulating cell cycle progression, signal transduction, and responding to cellular stress.
In this system, proteins destined for degradation are first tagged with a small protein called ubiquitin through a cascade of enzymatic reactions involving E1 (activating), E2 (conjugating), and E3 (ligating) enzymes. The polyubiquitin chain attached to target proteins serves as a signal for recognition by the 26S proteasome, a large protease complex that unfolds and degrades the tagged protein into short peptides.
Mechanism of Protein Tagging and Degradation (UPS)
Figure 1. Ubiquitin Proteasome System (UPS). Proteins are tagged with ubiquitin by the concerted actions of E1, E2 and E3 ligase enzymes. Ubiquitinated proteins are degraded by the proteasome or lysosome. Deubiquitinases (DUBs) can remove ubiquitins from proteins thereby altering their degradation or trafficking.
