Ubiquitin System

In the ubiquitin system, a target substrate is modified by ubiquitin or a ubiquitin-like protein. In most cases, proteins are modified by multiple moieties of ubiquitin, generating a polyubiquitin chain. This modification leads to their degradation by the 26S proteasome complex. Modification by a single moiety of ubiquitin can target proteins for degradation in the lysosome/vacuole. Modification by ubiquitin-like proteins serves nonproteolytic functions. Conjugation of ubiquitin is carried out by a modular cascade of enzymes, specific to each substrate. Ubiquitination of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that targets in a specific manner thousands of cellular proteins and plays major roles in a variety of basic pathways, such as cell division, differentiation, and quality control. Not surprisingly, aberrations in the system underlie the pathogenesis of many diseases, certain malignancies, and neurodegenerative disorders. Mechanism-based drugs are currently being developed.