Telomerase begins to reveal its secrets
One of the most mysterious components of the cell – the protein conglomerate telomerase – has become widely known for its participation in the formation of malignant neoplasms, aging processes and the maintenance of stem cells in an undifferentiated state.
Researchers and specialists of pharmaceutical companies are actively working on deciphering the structure of telomerase, but until recently, despite a lot of effort, except for two proteins discovered in 1999, they were unable to identify any of the components of this massive protein complex.
Scientists at Stanford University, working under the guidance of Dr. Steven Artandi, have identified two more proteins that are part of the telomerase complex, and have already received preliminary results regarding several more molecules. Since 1999, this discovery is the first major achievement in the study of the structure of telomerase. The authors claim that the discovery of previously unknown components of telomerase provides specialists with two new targets for cancer treatment.
Telomerase is known for its role in maintaining the stability of the genetic material of the cell. At each division, copies of each of the 46 chromosomes are synthesized in the cell. The originals and copies of the chromosomes are subsequently distributed between the two daughter cells. With each copy, the chromosome loses fragments of protective end sections – telomeres. Shortening of chromosomes is one of the causes of cell aging. After a certain number of divisions, the telomeres of the chromosomes are shortened to a critical length, and the cell stops dividing and dies.
Cancer cells solve this problem by synthesizing telomerase, which restores the lost end sections of chromosomes. As a result, cells acquire the ability to divide almost indefinitely. Under normal conditions, telomerase is active in the cells of the embryo, but soon after birth it disappears in almost all cells except adult stem cells and some cells of the immune system.
Since the discovery of telomerase in 1994, scientists have been hatching the idea of creating a drug that blocks this protein complex, which will lead to shortening of the chromosomes of cancer cells, their aging and death. However, the appearance of such a drug is impossible without sufficient information about the protein composition of telomerase.
One of the problems of studying telomerase is that even in actively dividing cancer cells it is contained in extremely small quantities. Until now, no technique has allowed analyzing such small amounts of protein.
To overcome this problem, the authors crushed a massive telomerase complex into tiny protein fragments and analyzed them on a particularly sensitive sequencer. The identified amino acid sequences were recoded into possible nucleotide sequences and compared with a genetic database in order to search for genes corresponding to each of the fragments.
As a result, the researchers were able to identify two genes encoding the protein components of telomerase – enzymes of the ATPase group, which were named pontin and reptin. Scientists say that the discoveries will not end there. In addition, using genetic methods, they managed to inactivate the synthesis of pontin, which led to the termination of the functioning of telomerase. In addition to working on further decoding of genes encoding telomerase components, the authors plan to search for small molecules that would suppress the activity of an already known protein in cancer cells.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
26.03.2008