Low-calorie diet, life extension and AMP-dependent kinase
Researchers at Stanford University have discovered that the enzyme AMP-dependent kinase (AMPK) plays an important role in regulating the early stages of the process of cell division in the human body. According to the data obtained by the authors, the reaction of this enzyme to nutrient deficiency can play an important role in the development of both normal and malignant cells.
According to the head of the study, Associate Professor Anne Brunet, her group has previously demonstrated that AMPK mediates the relationship between a low-calorie diet and longevity. This discovery prompted scientists to study the functions performed by this enzyme in the human body.
When working with human cells, researchers focused on studying the role of AMPK in mitosis, a process that ensures cell division with doubling of genetic material and its subsequent equivalent distribution between two daughter cells.
The AMP-dependent kinase molecule has a "pocket" that binds the donor molecule of the phosphate group. The enzyme regulates the activity of various proteins by modifying them with phosphate residues given by donor molecules. The main difficulty in identifying the target proteins of this enzyme is that the donor molecules labeled with a molecular label are too large for the pocket of the kinase molecule.
Scientists managed to overcome this problem by creating a modified version of the enzyme, the pocket size of the molecule of which allows it to bind to labeled donor molecules. This allowed them to conduct chemical screening in a living cell, which resulted in the identification of 32 proteins modified with labeled phosphate residues. 28 of them were not previously known to specialists as AMPK targets, and some of the new target proteins were involved in the process of cell division.
The participation of an enzyme mediating the body's response to nutrient deficiency in the regulation of cell division is quite logical, since in unfavorable conditions, the successful completion of mitosis without the appearance of genetic instability is a matter of exceptional importance.
Violation of AMPK activity or phosphorylation of regulatory subunit 12C (PPP1R12C)
interferes with the completion of the cell division cycle (figure from the article in Molecular Cell).
The researchers believe that the data they obtained extends to all dividing cells. They note that the identification of molecules regulating the activity of AMP-dependent kinase will increase the number of potential targets for the treatment of diseases such as cancer. Moreover, they believe that the screening system they have developed in a living cell will allow them to study the functioning of other enzymes.
Article by Banko et al. Chemical Genetic Screen for AMPKa2 Substrates Uncovers a Network of Proteins Involved in Mitosis published in the journal Molecular Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Stanford University Medical Center:
Study shows how nutrient levels affect enzyme associated with aging process.
14.12.2011