Wolf Prize Laureate in Medicine 2001
Affiliation at the time of the award:
California Institute of Technology, USA
“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 Alexander Varshavsky coming from a separate, more biological angle, began studies on histone protein modifications. His discovery that the ubiquitin-activating enzyme was defective in murine ts85 cells, provided the first important demonstration that the ubiquitin system plays an essential role in cell physiology. Soon thereafter, using yeast genetics, Varshavsky demonstrated that ubiquitin conjugation enzymes regulated DNA repair and cell cycle processes. These studies by Varshavsky demonstrated that the ubiquitin directed proteolysis system plays a key role in cellular regulation and provides biological significance to Hershko’s biochemistry.
The discovery by Hershko and Varshavsky that ubiquitin-dependent proteolysis is a fundamental regulatory process, impacts on virtually all aspects of modern biology.