The researchers found that the protein 'ubiquilin 4', which has a role in protecting against damage
In DNA, it is found in particularly high levels in tumors at an advanced stage, and its level may help determine the treatment. The article was recently published in the prestigious journal Cell
Researchers in the laboratory of Prof. Yossi Shilo in the Department of Human Molecular Genetics and Biochemistry in the Sackler Faculty of Medicine at Tel Aviv University discovered that a protein called ubiquilin 4, which takes part in the breakdown of proteins in the cell, is part of a complex system that repairs DNA breaks. They also found that the same protein is found in a higher than normal amount in cancer cells in an advanced stage of the disease. Following their findings, the researchers believe that the level of protein in different tumors may be used as an index to diagnose the condition of the patients and their chances of recovery, and even help doctors in determining a personal treatment protocol for different patients.
The research was carried out in Prof. Sheila's laboratory by Dr. Ron Yechimowitz, Dr. Yael Ziv and the doctoral student in Havana and La Pula, in collaboration with the laboratory of Prof. Christian Reinhardt from the University of Cologne in Germany. An article presenting the results of the research was published in January 2019 in the prestigious journal Cell, which is considered the leading journal in the world in the field of cell biology.
Genome Defense Army
"Preserving the stability of the genome has become a central issue in biomedical research in recent years, as an essential element in maintaining our health," says Prof. Sheila. "We know today that the DNA in our body cells is constantly attacked and damaged by a variety of factors: external factors, such as radiation, chemicals that pollute our environment, certain types of food and smoking; And also oxygen radicals that are continuously formed inside the cell. these vulnerabilities
DNA is a major cause of many different diseases, including cancer of all types, a variety of common chronic diseases, and even accelerated aging. Why and how, then, do most of us stay healthy most of the time? This, thanks to the sophisticated defense mechanisms activated in the healthy cell, which are constantly busy repairing the DNA damage, or in other words, maintaining the stability of the genome."
Prof. Sheila compares these defense mechanisms to an army: there is a limited regular army, numbering dozens of hard-working proteins, all of which are responsible for repairing DNA damage, and next to it is a reserve army of hundreds of proteins with different roles in the spaces of the cell, which are mobilized for the task in times of emergency - for example, when a tear occurs in -DNA.
In 1995, Prof. Sheila's laboratory discovered the winning protein for both the regular army and the recruitment of the 'reserve soldiers' who are keen to help repair DNA breaks, a protein named ATM. "Since then we have been investigating the principle of operation of ATM, and the way in which it mobilizes the various 'soldiers' from all over the cell into action, and we even discovered a number of such recruits," he says.
Recently, through a large-scale scan of the cell's proteins, the researchers discovered a new recruit to the system - a protein called ubiquilin 4. "Until now, it was known that ubiquilin 4 helps break down proteins in the cell, not necessarily in the context of genome stability. And here, we identified him as another one of ATM's subordinates in the DNA break repair system," says Prof. Sheila.
A valuable oncological index
Due to the close connection between the stability of the genome and the appearance of cancer, the researchers compared the level of the ubiquilin 4 protein in samples from malignant tumors, compared to healthy tissues taken from the same patients.
The researchers found that in some cases the amount of ubiquilin 4 in the tumor cells was significantly higher compared to healthy cells from the same patient. Further investigation revealed that the tumors in which a higher than normal level of ubiquilin 4 was observed are in the advanced stage of the disease. These are the tumors that have reached the aggressive stage, which has the potential to metastasize, and in addition - they have a higher resistance to certain chemotherapy treatments, as well as radiation treatments.
"From the findings we understood that although ubiquilin 4 participates in maintaining the stability of the genome, an increased amount of it actually undermines the response mechanism to DNA damage, which is built on delicate and precise checks and balances," explains Prof. Sheila. "In such a situation, it turns out that ubiquilin 4 actually supports the development of cancer, and even harms the effectiveness of conventional treatments. However, it turned out that such tumors are going to respond better to other chemotherapy treatments, which actually become more effective in cells with a high level of the protein."
This finding is of great importance at the clinical level: the researchers believe that ubiquilin 4 has the potential to be used as a valuable oncological index, indicating on the one hand the patient's condition and the extent of tumor progression at the time of diagnosis, and on the other hand - helping the doctor determine the appropriate treatment for the patient. In this way, the research provides an answer to one of the main challenges in cancer research today: the creation of biological markers that will help in the classification of malignancies and in planning the appropriate treatment, on an individual level.
"Our findings indicate that the gene that dictates the production of ubiquilin 4 may be a new oncogene - a gene that when its activity is increased, and the amount of the protein dictated by it increases - the cancer process is accelerated," concludes Prof. Sheila. "Today, our laboratory, in collaboration with Prof. Reinhardt's group, continues to investigate the roles of ubiquilin 4, mainly when it serves as a reservist in the branching system that maintains the stability of the genome. At the same time, we are expanding the range of malignant diseases in which we examine its level. All of this, in parallel with the continued search for additional 'soldiers' recruited by ATM for the genome damage repair system. Their number is estimated to be many hundreds, so fortunes have been made for this research."
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Peace,
How good it is to know that there is a mechanism in the body that protects the cells (ATM protein that detects situations and calls other proteins for help in repairing damage).
In my opinion, it is both interesting and terrible to know that some of those proteins such as ubiquilin 4 which is described in this article and which is known to transport the body and heals, changes its function and becomes a protein that transports to accelerate processes that are harmful to the body.
It is interesting what is the process that causes these proteins to change their function and whether the ATM which is responsible for them may also, in this or that state of the body, call for proteins that may accelerate harmful processes instead of healing the body.
Listen to me carefully - the scientists and doctors are the real heroes of this world... as far as I'm concerned... you will always be my superheroes, well done, keep it up.
Idan .
(:
Every time I see a picture of a prof in a lab coat I have to miss reading the article out of disgust. This is so not the case with these illustration photos with the robes in front of the laboratory bench. As if in the last twenty years they have touched a pipette. Dhilak Already in the postdoc you hardly move Eppendorf. That's what masters are for.
No illustration needed. It is possible to be satisfied with the scientific information without wrapping it in costumes. The white coat effect is accepted and works in the field of medicine. Let's leave it there