Worldwide interest in the research of Lasker Prize winners from the Technion
by Tamara Traubman
Photo: Avichai Nitzan
Prof. Aharon Chechanover and Prof. Avraham Hershko, yesterday at the Technion
Yesterday, a reception was held at the Technion in Haifa for the two Israeli researchers who recently won the "Laskar" prize for basic research in medicine - Prof. Avraham Hershko and Prof. Aharon Chachanover, both from the Technion's Faculty of Medicine.
The two - together with Prof. Alexander Varshavsky, from the California Institute of Technology (Caltech) who won the award with them - discovered in a long-term research work that proteins in the body intended for degradation are marked by a protein called ubiquitin. Their discoveries, reasoned the members of the prize committee, are of enormous importance.
The Lasker Prize, awarded by the American Lasker Foundation, is considered by scientists to be one of the most prestigious prizes in the world. In medicine, it is considered second in importance only to the Nobel Prize. Since it became known about the winning of the two, people in the science community often cite the statistics of the Lasker Prizes, which show that in recent years, most Lasker winners have also won the Nobel Prize after a few years.
The body's proteins break down all the time and new proteins are formed in their place. To illustrate, every week and a half almost all the proteins in the body are replaced by proteins
new ones The replacement process is of crucial importance in the development of the fetus, in the reproduction of cells, in the elimination of damaged proteins and in maintaining the normal activity of the body. The ubiquitin protein sticks to the proteins and serves as a "death signal", signaling that the time has come for a certain protein to break down and die.
"Their contribution is cardinal," says Prof. Haim Kahana, from the Department of Molecular Genetics at the Weizmann Institute. "They really founded the field. I think they are one of the few researchers in Israel who really opened up a scientific area that today is one of the most central."
Based on the researches of Prof. Hershko and Prof. Chakhanover, it was discovered in the years
The latter because disruptions in the operation of the ubiquitin system play an important role in causing a wide variety of diseases ranging from cancer to inflammatory processes, asthma and hypertension - says Prof. Yanon Ben-Naria, from the Lautenberg Center for Immunology at the School of Medicine of the Hebrew University and Hadassah.
Large pharmaceutical companies and scientists all over the world are currently investigating the ubiquitin system, hoping to find new and more effective ways to cure cancer and asthma. It is possible that in this way methods will be found that cause fewer side effects, because it will be possible to treat only the molecular root of the disease. Prof. Chechenover says that the prospect of finding a treatment for cervical cancer seems particularly encouraging - where, apparently, ubiquitin plays a crucial role.
"In the early XNUMXs, there were less than ten scientific articles a year on the subject," says Richard Kolka, professor of biochemistry at the Hebrew University, "today there are thousands of articles a year - which indicates the tremendous interest."
According to him, the protein breakdown mechanism in the cell was for a long time an unsolved problem. "Paradoxically, the protein production process, which is apparently a much more complex process, was solved a long time before they understood how proteins break down." At the end of the 60s, when the research began, most scientists were actually interested in the process of making proteins and not in breaking them down. "Perhaps a little courage was needed to explore something that was not in fashion," says Hershko.
Proteins are the workers of the body: for example, they tell cells when to be born and when to die, break down food and turn it into energy, transmit signals between cells, give skin elasticity and eyes their color. However, when a defective protein is produced, or when it is damaged, for example as a result of sunlight or air pollution, it does not perform its function correctly or does not perform it at all and therefore may cause disease. In such situations, the body needs a mechanism to destroy the damaged protein, so that it does not interfere with the normal activity of the body.
Proteins also have another very essential role and that is the control of cell culture. A complex control mechanism is responsible for the culture and the cessation of the cell culture, which operates with a very precise timing - any deviation in the timing can cause disease. So that the cells do not continue and multiply without control - and a cancerous tumor is formed - there are proteins that act as "brakes" that inhibit cell culture. But when the culture of cells is necessary, for example, during inflammation caused by an infection, ubiquitin molecules begin to accumulate on the "brake" proteins in the white blood cells (immune system cells), and signal to them that these proteins must be eliminated. Then, for a short time, the white blood cells multiply rapidly and fight the infection.
From preliminary studies, the possibility arises that ubiquitin also plays an important role in the activation of the immune system: it signals the enzymes to eliminate a part of a protein called - NF-kB. This part signals the immune system to act against unwanted guests that have invaded the body.
Ubiquitin does not recognize the proteins that need to be broken down. you work
The detection is carried out by a whole system of enzymes, which Prof. Chakhanover likens to glasses. Following them, the ubiquitin molecules arrive at the scene, pile up in a chain on top of the protein, and imprint on it the sign of death, signaling the cell's protein clearinghouse, the protease, to break down the protein. During degradation, the ubiquitin molecules separate and turn to issue death sentences to other proteins.
When the time comes for ubiquitin to die, says Prof. Chachanover, it is most likely marked by ubiquitin that lives. This process, he points out, has not yet been fully deciphered and is now the subject of fascinating research.
{Appeared in Haaretz newspaper, 31/10/2000{
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