Hershko, Avram (1937-…), a Hungarian-born Israeli biochemist, won a share of the 2004 Nobel Prize in chemistry for his research into a process that living cells use to break down proteins. The prize was also awarded to the biochemists Aaron Ciechanover of Israel and Irwin A. Rose of the United States. The three scientists studied a protein called ubiquitin. They discovered that ubiquitin can become attached to unwanted proteins inside the cell. Cellular structures called proteasomes then recognize this ubiquitin “tag” and destroy the unwanted proteins.
In a series of experiments during the late 1970’s and early 1980’s, Ciechanover, Hershko, and Rose determined how cells use ubiquitin to mark unwanted proteins. Their experiments showed that the process involves three major types of enzymes, which they referred to as E1, E2, and E3. First, an E1 enzyme attaches to ubiquitin and prepares it to bond with the unwanted protein. It then transfers the ubiquitin to an E2 enzyme. An E3 enzyme binds to the E2 enzyme and the unwanted protein and helps transfer the ubiquitin from the enzyme to the protein. This process repeats until a chain of several ubiquitins has been attached to the unwanted protein.
When the unwanted protein approaches a proteasome, the ubiquitin tag causes the opening of the proteasome to change shape. This enables the protein to enter the proteasome, where it is broken down. The ubiquitin is removed and returned to the cell to be used again.
Cells can produce hundreds of different E3 enzymes, each of which binds to different proteins. In this way, cells use ubiquitin to target specific proteins for destruction. Ciechanover, Hershko, and Rose’s work has helped scientists working to develop a new class of medicines for a variety of diseases, including cervical cancer and cystic fibrosis. These medicines target the ubiquitin binding process to stimulate the destruction of harmful proteins or to prevent the breakdown of necessary proteins.
Hershko was born in Karcag, Hungary, on Dec. 31, 1937. His family moved to Israel in 1950. In 1965, he earned an M.D. degree from the Hebrew University Hadassah Medical School in Jerusalem. Hershko served as a physician in the Israel Defense Forces from 1965 to 1967. He then returned to the Hadassah Medical School, earning a Ph.D. degree in medicine in 1969. From 1969 to 1971, he conducted research at the University of California at San Francisco. In 1972, he became a professor at the Technion-Israel Institute of Technology in Haifa.
