Orderlies at the cellular level
Researchers have found substances that prevent cell death
Natalia Bykova, ITEB RAS Press Service
What prevents the immune system from destroying tumor cells as effectively as other cells that are unnecessary to the body? In an experiment with cervical adenocarcinoma, a group of scientists from ITEB RAS found substances that destroy the natural mechanism of cell death. The results of the work are published in Cellular Signaling (Glukhova et al., Dephosphorylation of Fas-ligand and caveolin-1 is a preliminary step in Fas-ligand - caveolin-1 complex formation and cell death stimulation).
Cell death is a natural process. With its help, the body regulates the ratio of normal, working cells and those that have completed their life cycle. There are many reasons why certain microscopic "cells of life" die. They are known to science, but there is still no reliable answer as to how the mechanisms by which a cell launches a self-destruction program work in different scenarios. Penetration into these secrets will allow scientists to better understand the processes occurring in cells during their death, and this, in turn, will open up prospects for the development of new strategies for the treatment of diseases that have not yet submitted to modern medicine.
A group of scientists from the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences is studying the development of one of the variants of "cell suicide" – FasL-dependent cell death. Fas ligand (FasL) is a protein of the tumor necrosis factor family, a system that plays a key role in protecting the body from pathogens. It is necessary for the functioning of the immune system, suppression of excessive immune response of the body, destruction of damaged or transformed cells. Such an orderly at the cellular level.
Science knows something about how the Fas ligand works. It binds to the corresponding receptor on the surface of the target cells, which leads to the death of the cell carrying the receptor. It is also known that it can form a complex with another protein – caveolin-1, which is involved in the coordination of the interaction of different elements in the cell, and presumably in the prevention of tumor transformation of cells. Why do they remain inactive in a number of cases when cells degenerate into malignant ones?
"It is known that FasL and caveolin-1 can be phosphorylated. Based on this, it was suggested that protein phosphorylation may play a role in the development of FasL-dependent cell death," explains the author of the article, researcher at ITEB RAS Ksenia Glukhova. – In order to understand what this role is, we evaluated the effect of a number of substances that inhibit the action of two key groups of enzymes in the phosphorylation process – kinases and phosphatases. In our experiments, we evaluated how they affect the viability of the HeLa cervical adenocarcinoma cell line before and after activation of FasL synthesis. It turned out that their action destroys the natural mechanism of cell death: phosphorylation of the tyrosine residues of the Fas ligand and caveolin-1 prevents the development of FasL-dependent cell death. In addition, it has been shown that tyrosine kinase p59Fyn may be responsible for phosphorylation of FasL."
Scheme of interaction of caveolin-1, p59Fyn and FasL.
The results obtained may be useful for explaining the mechanisms of action of existing therapeutic kinase or phosphatase inhibitors and to identify new molecular targets in antitumor therapy.
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