Romero AL, Guerra SG, Luqueño BOI, Pardo JP

Idioma: Español
Referencias bibliográficas: 35
Paginas: 4-13
Archivo PDF: 1801.93 Kb.

RESUMEN

El complejo proteico blanco de la rapamicina (TORC) participa en la regulación del crecimiento y de varios aspectos del metabolismo celular, tales como: síntesis de fosfolípidos, biogénesis de los ribosomas, incremento de la síntesis de RNAm y de proteínas e inhibición de la autofagia. Su actividad se regula por diversas señales generadas por nutrientes, factores de crecimiento y oxígeno, entre otras. Al entrar estas moléculas a la célula modifican la actividad de TORC, quien se encarga de amplificar la señal. La importancia del complejo radica en que es el núcleo integrador de una amplia gama de señales necesarias para un adecuado metabolismo celular. Se revisará brevemente las funciones de TORC en la regulación del metabolismo celular y su conservación desde levaduras a mamíferos.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Betz C, Hall MN (2013) Where is mTOR and what is it doing there? Journal of Cell Biology 203: 563-574.

2. Weisman R, Cohen A, Gasser SM (2014) TORC2-a new player in genome stability. Embo Molecular Medicine 6: 995-1002.

3. Cornu M, Albert V, Hall MN (2013) mTOR in aging, metabolism, and cancer. Current Opinion in Genetics & Development 23: 53-62.

4. Maegawa K, Takii R, Ushimaru T, Kozaki A (2015) Evolutionary conservation of TORC1 components, TOR, Raptor, and LST8, between rice and yeast. Molecular Genetics and Genomics 290: 2019-2030.

5. Benjamin D, Colombi M, Moroni C, Hall MN (2011) Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov 10: 868-880.

6. Groenewoud MJ, Zwartkruis FJT (2013) Rheb and Rags come together at the lysosome to activate mTORC1. Biochemical Society Transactions 41: 951-955.

7. Adami A, Garcia-Alvarez B, Arias-Palomo E, Barford D, Llorca O (2007) Structure of TOR and its complex with KOG1. Mol Cell 27: 509- 516.

8. Loewith R, Hall MN (2011) Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics 189: 1177-1201.

9. Asnaghi L, Bruno P, Priulla M, Nicolin A (2004) mTOR: a protein kinase switching between life and death. Pharmacol Res 50: 545-549.

10. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, et al. (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Molecular Cell 10: 457-468.

11. Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 127: 5-19.

12. Laxman S, Tu BP (2011) Multiple TORC1- associated proteins regulate nitrogen starvation-dependent cellular differentiation in Saccharomyces cerevisiae. PLoS One 6: e26081.

13. Gaubitz C, Oliveira TM, Prouteau M, Leitner A, Karuppasamy M, et al. (2015) Molecular Basis of the Rapamycin Insensitivity of Target Of Rapamycin Complex 2. Mol Cell 58: 977-988.

14. Gaubitz C, Prouteau M, Kusmider B, Loewith R (2016) Torc2 Structure and Function. Trends in Biochemical Sciences 41: 532-545.

15. Gaubitz C, Oliveira TM, Prouteau M, Leitner A, Karuppasamy M, et al. (2015) Molecular Basis of the Rapamycin Insensitivity of Target Of Rapamycin Complex 2. Molecular Cell 58: 977-988.

16. Khanna A, Lotfi P, Chavan AJ, Montano NM, Bolourani P, et al. (2016) The small GTPases Ras and Rap1 bind to and control TORC2 activity. Scientific Reports 6.

17. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265-275.

18. Inoki K, Ouyang H, Li Y, Guan KL (2005) Signaling by target of rapamycin proteins in cell growth control. Microbiology and Molecular Biology Reviews 69: 79-+.

19. Avruch J, Hara K, Lin Y, Liu M, Long X, et al. (2006) Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase. Oncogene 25: 6361-6372.

20. Xiong Y, Sheen J (2014) The role of target of rapamycin signaling networks in plant growth and metabolism. Plant Physiol 164: 499-512.

21. Janes MR, Limon JJ, So LM, Chen J, Lim RJ, et al. (2010) Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nature Medicine 16: 205-U115.

22. Ikai N, Nakazawa N, Hayashi T, Yanagida M (2011) The reverse, but coordinated, roles of Tor2 (TORC1) and Tor1 (TORC2) kinases for growth, cell cycle and separase-mediated mitosis in Schizosaccharomyces pombe. Open Biology 1.

23. Schneper L, Duvel K, Broach JR (2004) Sense and sensibility: nutritional response and signal integration in yeast. Curr Opin Microbiol 7: 624-630.

24. Tehlivets O, Scheuringer K, Kohlwein SD (2007) Fatty acid synthesis and elongation in yeast. Biochim Biophys Acta 1771: 255-270.

25. Bozaquel-Morais BL, Madeira JB, Maya- Monteiro CM, Masuda CA, Montero-Lomeli M (2010) A new fluorescence-based method identifies protein phosphatases regulating lipid droplet metabolism. PLoS One 5: e13692.

26. Shen Y, Volrath SL, Weatherly SC, Elich TD, Tong L (2004) A mechanism for the potent inhibition of eukaryotic acetyl-coenzyme a carboxylase by soraphen A, a macrocyclic polyketide natural product. Molecular Cell 16: 881-891.

27. Madeira JB, Masuda CA, Maya-Monteiro CM, Matos GS, Montero-Lomeli M, et al. (2015) TORC1 Inhibition Induces Lipid Droplet Replenishment in Yeast. Molecular and Cellular Biology 35: 737-746.

28. Sengupta S, Peterson TR, Sabatini DM (2010) Regulation of the mTOR Complex 1 Pathway by Nutrients, Growth Factors, and Stress. Molecular Cell 40: 310-322.

29. Tan VP, Miyamoto S (2016) Nutrient-sensing mTORC1: Integration of metabolic and autophagic signals. Journal of Molecular and Cellular Cardiology 95: 31-41.

30. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, et al. (2010) Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141: 290-303.

31. Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, et al. (2016) METABOLISM Sestrin2 is a leucine sensor for the mTORC1 pathway. Science 351: 43-48.

32. Goberdhan DCI, Wilson C, Harris AL (2016) Amino Acid Sensing by mTORC1: Intracellular Transporters Mark the Spot. Cell Metabolism 23: 580-589.

33. Chantranupong L, Scaria SM, Saxton RA, Gygi MP, Shen K, et al. (2016) The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. Cell 165: 153-164.

34. Meric-Bernstam F, Gonzalez-Angulo AM (2009) Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 27: 2278-2287.

35. Laplante M, Sabatini DM (2009) mTOR signaling at a glance. Journal of Cell Science 122: 3589-3594.