Death in installments
Russian biologists have found a way to "postpone" cell death
Biologists from MSU and The Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences has found out how to stop the self-destruction program in human cells. This will help in the creation of cancer drugs, according to an article published in the journal Cell Death & Disease (Glukhova et al., Impairment of Fas-ligand–caveolin-1 interaction inhibits Fas-ligand translation to rafts and Fas-ligand-induced cell death).
The genomes of humans and other multicellular creatures contain several sets of genes with special "instructions" for the self-destruction of cells under certain conditions. For example, such a "programmed suicide", or apoptosis in the language of science, occurs when the DNA of a cell is damaged, viruses penetrate into its nucleus and in some other situations when it is necessary for the survival of the organism as a whole. Many of these reactions are triggered not by themselves, but as a result of contact of the cell shell with special signaling molecules, explained Vladimir Gogvadze, an employee of the Faculty of Fundamental Medicine of Moscow State University. This allows the immune system to kill "rebellious" cells that can become the progenitors of cancerous tumors.
Tumblers of Death
Russian biologists have studied the work of one of these "tumblers of death" – FasL protein (one of the cytokines of the family of tumor necrosis factors – VM). There are a lot of its molecules both on the shell of human cells and inside them. Despite the fact that the structure of FasL is well studied, scientists did not know which signaling molecules cause it to kill the cell. Even more precisely, it was unclear how the protein is located inside the membrane and interacts with the internal contents of the cell.
Russian researchers have managed to close this gap in biology. They found out how FasL can be used to "inhibit" the process of cell death. This became possible thanks to experiments on a special line of cancer cells grown in the laboratories of Moscow State University and ITEB RAS. The DNA of these cells was modified so that they could be forced to produce huge amounts of FasL or completely stop protein synthesis. Manipulations helped to understand the mechanism of apoptosis.
Experiments have shown that for the "suicide button" to work, another protein is needed – caveolin-1. It is present in the membranes of human cells and plays an important role in the work of special sites – caveoles. It is there that signal molecules coming from the external environment are collected and read.
Caveolin-1 plays an important role in triggering apoptosis: inside FasL there is a kind of "landing place" for caveolin, the removal of which disables the cellular suicide program. This happens even at very high concentrations of both proteins.
It is noteworthy that the scheme also works with many other proteins that are responsible for triggering apoptosis.
The discovery is particularly interesting in the context of the fight against cancer, whose cells lose the ability to destroy themselves. Scientists hope that further study of caveolin, FasL and other "death proteins" will help to understand how to forcibly include them in cancer cells. And as a result – to destroy cancer cells without affecting healthy tissues.
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