As a graduate student with Dr. Avram Hershko and in collaboration with Dr. Irwin A. Rose from the Fox Chase Cancer Center in Philadelphia, USA, they discovered that covalent attachment of ubiquitin to a target protein signals it for degradation. They deciphered the mechanism of conjugation, described the general proteolytic functions of the system, and proposed a model according to which this modification serves as a recognition signal for a specific downstream protease. With the discovery of the numerous functions of the system, in particular, those involved with maintaining the quality of the cellular proteome, the system has become a broad platform for drug targeting, especially in malignancies, and more recently in neurodegeneration.
