mTOR СИГНАЛ ЖОЛЫНЫҢ ЖОҒАРҒЫ АҒЫНДЫҚ РЕТТЕУШІЛЕРІ
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Keywords:
mTOR, protein kinase,Abstract
mTOR is a protein kinase belongs to the family of phosphoinositide-3-kinase (PI3K)-related kinases (PIKKs). mTOR exists in two distinct complexes called complex 1 (mTORC1) and complex 2 (mTORC2). Due to their different protein compositions, the mTOR complexes have important differences in their sensitivities to rapamycin, in the upstream signals they integrate, in the substrates they regulate, and in the biological processes they control. Cell growth and proliferation are orchestrated by signaling networks in response to environmental cues such as nutrients, growth factors, hormones, intracellular and extracellular energy status, and stress conditions. mTOR signaling pathway is a central regulator in a diverse array of vital cellular processes, including proliferation, growth, differentiation, and survival. TOR (target of rapamycin) protein kinase is an evolutionarily conserved regulator in these signaling networks. Because of the mTOR is linked to the PI3K/PTEN/Akt/TSC signaling pathway, it is the main cause for development of a wide variety of cancers and other diseases.References
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7. Kunz, J., Henriquez, R., et al. Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell (1993); 73: 585-596
8. Chiu, M.I., Katz, H., Berlin, V. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. Proc Natl Acad Sci USA (1994); 91:12574-12578.
9. Guertin, D.A., Sabatini, D.M. The pharmacology of mTOR inhibition. Science Signaling (2009); 2: pe24.
10. Feldman, M.E., Apsel, B., Uotila, A., et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol (2009); 7(2): 0371-0383.
11. Yip, C.K., Murata, K., et al. Structure of the human mTOR complex I and its implications for rapamycin inhibition. Molecular Cell (2010); 38: 768-774.
12. Sengupta, S., Peterson, T.R., Sabaitni, D.M. Regulation of the mTOR Complex I Pathway by Nutrients, Growth Factors, and Stress. Molecular Cell (2010); 40(2): 310-322.
13. Sarbassov, D.D. and Sabatini, D.M. Redox regulation of the nutrient-sensitive Raptor-mTOR pathway complex. J. Biol. Chem. (2005); 280:39505-39509.
14. Kim, D.H., Sarbassov, D.D., Ali, S.M., et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the growth machinery. Cell (2002); 110: 163-175.
15. Simon, J.C., Simon, J.M. Nutrient-responsive mTOR signalling grows on Sterile ground. Biochem. J. (2007); 403:e1–e3.
16. Kim, E. Mechanisms of amino acid sensing in mTOR signaling pathway. Nutrition Research and Practice (2009); 3(1): 64-71.
17. Sancak, Y., Bar-Peled, L., et al. Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino Acids.Cell (2010); 141:290-303.
18. Sancak, Y., Peterson, T.R., Shaul, Y.D., et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science (2008); 320: 1496–1501.
19. Kalaany, N.Y., Sabatini, D.M. Tumours with PI3K activation are resistant to dietary restriction. Nature (2009); 458: 725-731.
20. Inoki, K., Ouyang, H., Zhu, T., et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell (2006); 126: 955-968.
21. Reiling, J. H., Sabatini, D. M., Increased mTORC1 signaling UPRegulates stress. Mol. Cell (2008); 29: 533–535.
22. Miriam S., Dana, L. TOR Complex 2 Controls Gene Silencing, Telomere Length Maintenance, and Survival under DNA-Damaging Conditions. Mol. and Cell. Biol., (2009); 4584–4594.
23. Leif, W. E. Growth Control Under Stress: mTOR Regulation through the REDD1-TSC Pathway. Cell Cycle (2005); 4(11): 1500-1502.
2. Guertin, D.A., and Sabatini, D.M. Defining the role of mTOR in cancer. Cancer Cell (2007); 12: 9–22.
3. Берсимбай Р.И., Булгакова О.В., Омаров Р.Т., Сарбасов Д. Роль mTOR сигнальной системы в регуляции клеточных функций. Доклады НАН РК (2010); 5, c. 82-90.
4. Bulgakova O.V., Shaikenov T., Bersimbay R.I., Sarbassov D.D. Purification of the mTOR complexes by affinity chromathography. Reports of the international conference: III Humboldt-Kolleg, Astana, Kazakhstan (2010); 45-46.
5. Булгакова О.В., Берсимбаев Р.И., Сарбасов Д.С. Регуляция mTOR сигнального пути. Материалы 15 международного курса Александра Холлендера: Взаимодействие генома и окружающей среды,
генетическая токсикология (2009); c. 69-70.
6. Eric, J.B., Mark, W.A., et al. A mammalian protein targeted by G1-arresting rapamycin–receptor complex. Nature (1994); 369: 756 – 758.
7. Kunz, J., Henriquez, R., et al. Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell (1993); 73: 585-596
8. Chiu, M.I., Katz, H., Berlin, V. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. Proc Natl Acad Sci USA (1994); 91:12574-12578.
9. Guertin, D.A., Sabatini, D.M. The pharmacology of mTOR inhibition. Science Signaling (2009); 2: pe24.
10. Feldman, M.E., Apsel, B., Uotila, A., et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol (2009); 7(2): 0371-0383.
11. Yip, C.K., Murata, K., et al. Structure of the human mTOR complex I and its implications for rapamycin inhibition. Molecular Cell (2010); 38: 768-774.
12. Sengupta, S., Peterson, T.R., Sabaitni, D.M. Regulation of the mTOR Complex I Pathway by Nutrients, Growth Factors, and Stress. Molecular Cell (2010); 40(2): 310-322.
13. Sarbassov, D.D. and Sabatini, D.M. Redox regulation of the nutrient-sensitive Raptor-mTOR pathway complex. J. Biol. Chem. (2005); 280:39505-39509.
14. Kim, D.H., Sarbassov, D.D., Ali, S.M., et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the growth machinery. Cell (2002); 110: 163-175.
15. Simon, J.C., Simon, J.M. Nutrient-responsive mTOR signalling grows on Sterile ground. Biochem. J. (2007); 403:e1–e3.
16. Kim, E. Mechanisms of amino acid sensing in mTOR signaling pathway. Nutrition Research and Practice (2009); 3(1): 64-71.
17. Sancak, Y., Bar-Peled, L., et al. Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino Acids.Cell (2010); 141:290-303.
18. Sancak, Y., Peterson, T.R., Shaul, Y.D., et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science (2008); 320: 1496–1501.
19. Kalaany, N.Y., Sabatini, D.M. Tumours with PI3K activation are resistant to dietary restriction. Nature (2009); 458: 725-731.
20. Inoki, K., Ouyang, H., Zhu, T., et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell (2006); 126: 955-968.
21. Reiling, J. H., Sabatini, D. M., Increased mTORC1 signaling UPRegulates stress. Mol. Cell (2008); 29: 533–535.
22. Miriam S., Dana, L. TOR Complex 2 Controls Gene Silencing, Telomere Length Maintenance, and Survival under DNA-Damaging Conditions. Mol. and Cell. Biol., (2009); 4584–4594.
23. Leif, W. E. Growth Control Under Stress: mTOR Regulation through the REDD1-TSC Pathway. Cell Cycle (2005); 4(11): 1500-1502.
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Қазыкен, Д., Берсімбай, Р. І., & Сарбассов, Д. Д. (2015). mTOR СИГНАЛ ЖОЛЫНЫҢ ЖОҒАРҒЫ АҒЫНДЫҚ РЕТТЕУШІЛЕРІ. Experimental Biology, 53(1), 23–27. Retrieved from https://bb.kaznu.kz/index.php/biology/article/view/237
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BIOTECHNOLOGY, BIOCHEMISTRY AND PLANTS PHYSIOLOGY
