Wolf Prize Laureate in Medicine 2001
Affiliation at the time of the award:
Technion – Israel Institute of Technology, Israel
“for the discovery of the ubiquitin system of intracellular protein degradation and the crucial functions of this system in cellular regulation”.
Hershko and Varshavsky stand out in their seminal contributions to the discovery of both the mechanism and the functions of ubiquitin-dependent proteolysis.
Professor Avram Hershko was the first to recognize that the covalent attachment of a small protein, later found to be ubiquitin, plays a role in ATP-dependent proteolysis. Over the following several years, along with his co-workers, Hershko elucidated the three-step mechanism of ubiquitination, which involves the ubiquitin-activating (E1) enzyme, that forms a thioester linkage to ubiquitin, a ubiquitin-conjugating (E2) enzyme, that transfers ubiquitin to the target protein, and the E3 component, required for recognizing the protein target. This elegant and rigorous biochemical analysis provided the framework for subsequent studies of the role of ubiquitin in regulated proteolysis.
The discovery by Hershko and Varshavsky that ubiquitin-dependent proteolysis is a fundamental regulatory process, impacts on virtually all aspects of modern biology.