Avram Hershko

(1937- )

Dr. Avram Hershko was born in 1937, in Karcag, Hungary. In 1950, Hershko and his family emigrated from Hungary to Israel. Hershko is a Distinguished Professor at the Unit of Biochemistry, the Rappaport Faculty of Medicine at the Technion (Israel Institute of Technology) in Haifa, Israel. He became a Professor at the Technion in 1980, and was an Associate Professor there from 1972 to 1980.

In 1969-72, Hershko was a postdoctoral fellow with the late Dr. Gordon Tomkins at the University of California, San Francisco. Hershko holds Ph. D. and M. D. D. degrees. He did his graduate work in 1967-69 at the Hadassah Medical School of the Hebrew University in Jerusalem, receiving a Ph. D. degree in 1969. Hershko received an M. D. degree in 1965, at the same Medical School. In 1965-67, Hershko worked as a physician in the Israel Defense Forces.

Hershko shared the 2004 Nobel Prize in Chemistry with Irwin Rose and Aaron Ciechanover for “for the discovery of ubiquitin-mediated protein degradation.” The following press release from the Royal Swedish Academy of Sciences describes Hershko's work:

Proteins build up all living things: plants, animals and therefore us humans. In the past few decades biochemistry has come a long way towards explaining how the cell produces all its various proteins. But as to the breaking down of proteins, not so many researchers were interested. Aaron Ciechanover, Avram Hershko and Irwin Rose went against the stream and at the beginning of the 1980s discovered one of the cell's most important cyclical processes, regulated protein degradation. For this, they are being rewarded with this year's Nobel Prize in Chemistry.

Aaron Ciechanover, Avram Hershko and Irwin Rose have brought us to realise that the cell functions as a highly-efficient checking station where proteins are built up and broken down at a furious rate. The degradation is not indiscriminate but takes place through a process that is controlled in detail so that the proteins to be broken down at any given moment are given a molecular label, a ‘kiss of death', to be dramatic. The labelled proteins are then fed into the cells' "waste disposers", the so called proteasomes, where they are chopped into small pieces and destroyed.

The label consists of a molecule called ubiquitin. This fastens to the protein to be destroyed, accompanies it to the proteasome where it is recognised as the key in a lock, and signals that a protein is on the way for disassembly. Shortly before the protein is squeezed into the proteasome, its ubiquitin label is disconnected for re-use.

Thanks to the work of the three Laureates it is now possible to understand at molecular level how the cell controls a number of central processes by breaking down certain proteins and not others. Examples of processes governed by ubiquitin-mediated protein degradation are cell division, DNA repair, quality control of newly-produced proteins, and important parts of the immune defence. When the degradation does not work correctly, we fall ill. Cervical cancer and cystic fibrosis are two examples. Knowledge of ubiquitin-mediated protein degradation offers an opportunity to develop drugs against these diseases and others.

Honors & Awards
1987 - Weizmann Prize for Sciences (Israel)
1993 - Elected to the European Molecular Biology Organization
1994 - Israel Prize in Biochemistry and Medicine
1999 - Wachter Prize, by the University of Innsbruck, Austria (with A. Ciechanover)
1999 - Gairdner International A ward, by the Gairdner Foundation, Canada (with A. Varshavsky)
2004 - Nobel Prize in Chemistry

Most relevant publications by Avram Hershko

Ciechanover, A., Hod, Y., and Hershko, A. (1978) A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. Biochem. Biophys. Res. Commun. 81, 1100-1105.

Hershko, A., Ciechanover, A., Heller, H., Haas, A. L., and Rose, I. A. (1980) Proposed role of ATP in protein breakdown: conjugation of proteins with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc. Natl. Acad. Sci. USA 77, 1783-1786.

Ciechanover, A., Elias, S., Heller, H. and Hershko, A. (1982) Covalent affinity purification of ubiquitin-activating enzyme. J. Biol. Chem. 257, 2537-2542.

Hershko, A., Heller, H., Elias, S. and Ciechanover, A. (1983) Components of ubiquitin-protein ligase system: resolution, affinity purification and role in protein breakdown. J. Biol. Chem. 258, 8206-8214.

Hershko, A., Leshinsky, E., Ganoth, D. and Heller, H. (1984) ATP-dependent degradation of ubiquitin-protein conjugates. Proc. Natl. Acad. Sci. USA 81, 1619-1623.

Hershko, A., Heller, H., Eytan, E. and Reiss, Y. (1986) The protein substrate binding site of the ubiquitin-protein ligase system. J. Biol. Chem. 261, 11992-11999.

Ganoth, D., Leshinsky, E., Eytan, E., and Hershko, A. (1988) A multicomponent system that degrades proteins conjugated to ubiquitin. Resolution of components and evidence for ATP-dependent complex formation. J. Biol. Chem. 263, 12412-1241.