Cell tags: proteins of the "death program" will help create drugs for diabetes and cancer

For the first time, scientists from Moscow State University have described the properties and functions of one of the proteins that regulate cell death. There is a special "death program" in the human body that is triggered to destroy damaged or "spent" cells. The BMF protein, which has been comprehensively studied in the work of specialists, belongs to the group of those that control the activation of this program and determine the fate of cells both under normal conditions and in various pathologies. In the future, the data obtained and systematized will help create new drugs and treatments for cancer, diabetes and other diseases, experts told Izvestia.

How is cell death regulated?

The staff of the Faculty of Fundamental Medicine of the Lomonosov Moscow State University (MSU FFM) and the V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences (IMB RAS) analyzed the scientific literature and for the first time in the world characterized the features of the structure and functioning of the BMF protein from the Bcl-2 family.

— There is a special "death program" in every cell of the human body, which is launched to destroy damaged or spent cells. The BMF protein, which was comprehensively studied in our work, belongs to the Bcl-2 family group, which control the activation of this program and determine the fate of cells both under normal conditions and in various pathologies," Nikolai Pervushin, a researcher at the FFM Moscow State University, told Izvestia.

Photo: MSU

The scientist noted that within the Bcl-2 family there are two opposing groups of proteins: some trigger the "death program" (these include the studied BMF), while others block it and help cells survive. Such a two-level system allows you to fine-tune the processes of body tissue renewal: only defective or unnecessary ones die, while healthy ones remain.

When stressful conditions occur (for example, when the genetic apparatus of cells is damaged), complex molecular cascades are activated that destroy structural components, eventually leading to cell death. The BMF protein is actively involved in this process, which blocks the work of its "relatives" in the Bcl-2 family, responsible for cell survival, the specialist said.

Photo: MSU

—Failures in the cell life and death control system, including due to the malfunction of the BMF protein, lead to the occurrence or progression of various diseases," said Gelina Kopeina, a leading researcher at the MSU FFM and head of the Laboratory of Cell Death Mechanisms at the Institute of Biological Sciences of the Russian Academy of Sciences. — For example, avoiding the death of cells with various disorders and their subsequent uncontrolled reproduction leads to the emergence and progression of cancer, which can occur at low levels of BMF or in the case of suppression of its functional activity.

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This compound plays an important role in destroying cells that are in the wrong place, preventing the spread of tumors throughout the body. However, the opposite picture is also possible, when the intracellular content of this protein is increased and the cells die too intensively. If this process occurs in the pancreas, it can contribute to the development of diabetes mellitus.

— In our work, all possible functions of the BMF protein, as well as ways of its regulation in cells, were described in detail. To date, a whole class of drugs has been developed that are able to control the work of certain proteins of its family, one of which (Venetoclax) is already being used to treat patients with chronic lymphocytic leukemia. These drugs block proteins responsible for cell survival, which in turn ensures unhindered operation of proteins that launch the "death program," said Gelina Kopeina.

In a new scientific article, scientists have identified various antitumor agents that activate this protein and depend on its content in cells.

BMF plays an important role in regulating the process of apoptosis (programmed cell death), Yegor Prokhorchuk, a genetic scientist, Doctor of Biological Sciences and chief researcher at the Institute of Biotechnology of the Russian Academy of Sciences, told Izvestia. According to the geneticist, the BMF protein can be used to diagnose and prevent cancer.

— The use of antibodies to BMF can serve as a marker for the early diagnosis of certain types of cancer. For example, prostate cancer, pancreatic cancer, or follicular lymphoma," he noted.

According to the expert, BMF can also be used in the development of new treatments for type 2 diabetes and other endocrine diseases.

Photo: IZVESTIA/Anna Selina

The studied protein helps the body to remove damaged cells in time and contain tumor metastases. However, excessive activity can, on the contrary, harm — for example, contribute to the loss of insulin-producing beta cells in diabetes, said the head of the Center of Excellence "Personalized Medicine" Kazan (Volga Region) Federal University.

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"The study will allow us to create more precisely targeted antitumor drugs of the BH3 mimetic class and their combinations in order to "unlock" the natural cell death program in the tumor. Secondly, tissue protection products. For example, molecules or peptides that temporarily "turn off" BMF where cell death is excessive (diabetes, neurodegeneration). Third, new diagnostic markers. The level and activity of these proteins can be used to select personal therapy and predict the response to treatment," the expert said.

Photo: IZVESTIA/Sergey Lantyukhov

Aging and cell death are a natural process, and programmed cell death is subtly controlled so that different contexts determine different outcomes, said Mikhail Bolkov, a researcher at the Institute for the Study of Aging at the Russian Gerontological Research and Clinical Center at Pirogov University.

— Programmed cell death — apoptosis — is regulated at different levels. And there are many different mechanisms that allow, accelerate or cancel cell death "at the very last moment" — these are precisely the proteins of the Bcl-2 family. In this study, the researchers examined in detail the role of one of these previously underestimated BMFS. The protein has its own potential, and the ways of its application, possibilities and limitations are the task of future research," the scientist said.

The study, supported by a grant from the Russian Science Foundation (RSF), has been published in the scientific journal Cell Death and Differentiation.