Rapamycin target: study continues

NanoNewsNet based on the materials of the Biozentrum of the University of Basel:
New Insights into the Signaling Network of the Vital Protein mTORDisorders in the metabolic pathway of the mTOR protein are caused by many diseases, and accurate knowledge of individual links in the signaling network of this protein can give scientists powerful tools in the fight against these diseases, in particular, new therapeutic targets.

The research group of Professor Michael Hall from the Biocenter of the University of Basel, Switzerland, has identified a number of new mTOR-regulated proteins, including an enzyme necessary for the synthesis of DNA building blocks.

The results of the study by Professor Hall and his colleagues have just been published in the journal Science (Robitaille et al., Quantitative Phosphoproteomics Reveal mTORC1 Activates de Novo Pyrimidine Synthesis).

Mammalian target of rapamycin (mTOR) controls the processes that are of fundamental importance for the body – the growth and survival of cells, their migration and metabolism. As a key component of two complexes, mTORC1 and mTORC2, it stimulates the production of proteins and fats and ensures that sufficient energy is supplied to the cell. Disorders in the finely regulated mTOR signaling network are directly related to the development of serious diseases such as cancer, diabetes and cardiovascular diseases. The search for previously unknown mTOR–regulated proteins is the basis for the development of new approaches to the treatment of these ailments.

Given the enormous importance of mTOR in cell physiology, scientists suspect that many proteins and processes controlled by this protein kinase have not yet been established. With the help of one of the most advanced technologies, the so-called quantitative phosphoproteomics, Professor Hall's research group was able to identify more than 300 new proteins that are targets of mTOR, with a wide range of functions.

In particular, the researchers found out exactly how mTORC1 controls the growth and reproduction of cells: the protein stimulates the formation of nucleotides – the building blocks of genetic material (DNA and RNA) synthesized in multistage processes from simpler molecules.

The first stages of nucleotide biosynthesis are mediated by the enzyme CAD (carbamoyl-phosphate synthetase 2), and mTORC1 enhances the union of several molecules of this enzyme into oligomers, thereby enhancing CAD activity and nucleotide synthesis.

Regulatory protein complex mTORC1
promotes oligomerization of the CAD enzyme.
CAD oligomers are shown in green, DNA is shown in blue.
(Photo: University of Basel/Biozentrum)

Although the piggy bank of knowledge about the mTOR protein is constantly being updated, the data obtained by Swiss researchers suggest that a lot about its functions remains unknown. A comprehensive study of the mTOR-controlled signaling pathways, as well as the consequences of violations of its signaling, is extremely important for understanding pathological processes and developing new therapeutic approaches. The research of Professor Hall and his colleagues helped to unravel another link in the chain of mysteries of mTOR.

Portal "Eternal youth" http://vechnayamolodost.ru25.02.2013