Felix Hoppe-Seyler Lecture 2000. The ubiquitin system and the N-end rule pathway

Eukaryotes contain a highly conserved multienzyme system which covalently links a small protein, ubiquitin, to a variety of intracellular proteins that bear degradation signals recognized by this system. The resulting ubiquitin-protein conjugates are degraded by the 26S proteasome, an ATP-dependent protease. Pathways that involve ubiquitin play major roles in a huge variety of processes, including cell differentiation, cell cycle, and responses to stress. In this article we briefly review the design of the ubiquitin system, and describe two recent advances, the finding that ubiquitin ligases interact with specific components of the 26S proteasome, and the demonstration that peptides accelerate their uptake into cells by activating the N-end rule pathway, one of several proteolytic pathways of the ubiquitin system.