Skip to main content
Have a personal or library account? Click to login
ER Stress Activates the TOR Pathway through Atf6 Cover

ER Stress Activates the TOR Pathway through Atf6

By:  and    
Open Access
|Apr 2018

References

  1. Wang, S and Kaufman, RJ. The impact of the unfolded protein response on human disease. J Cell Biol. 2012; 197: 857867. DOI: 10.1083/jcb.201110131
  2. Wu, J and Kaufman, RJ. From acute ER stress to physiological roles of the Unfolded Protein Response. Cell Death Differ. 2006; 13: 374384. DOI: 10.1038/sj.cdd.4401840
  3. Walter, P and Ron, D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011; 334: 10811086. DOI: 10.1126/science.1209038
  4. Korennykh, AV, Egea, PF, Korostelev, AA, Finer-Moore, J, Zhang, C, et al. The unfolded protein response signals through high-order assembly of Ire1. Nature. 2009; 457: 687693. DOI: 10.1038/nature07661
  5. Hollien, J and Weissman, JS. Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science. 2006; 313: 104107. DOI: 10.1126/science.1129631
  6. Yoshida, H, Matsui, T, Yamamoto, A, Okada, T and Mori, K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2001; 107: 881891. DOI: 10.1016/S0092-8674(01)00611-0
  7. Calfon, M, Zeng, H, Urano, F, Till, JH, Hubbard, SR, et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature. 2002; 415: 9296. DOI: 10.1038/415092a
  8. Harding, HP, Zhang, Y and Ron, D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 1999; 397: 271274. DOI: 10.1038/16729
  9. Krishnamoorthy, T, Pavitt, GD, Zhang, F, Dever, TE and Hinnebusch, AG. Tight binding of the phosphorylated alpha subunit of initiation factor 2 (eIF2alpha) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation. Mol Cell Biol. 2001; 21: 50185030. DOI: 10.1128/MCB.21.15.5018-5030.2001
  10. Hershey, JW, Sonenberg, N and Mathews, MB. Principles of translational control: an overview. Cold Spring Harb Perspect Biol. 2012; 4. DOI: 10.1101/cshperspect.a011528
  11. Ye, J, Rawson, RB, Komuro, R, Chen, X, Dave, UP, et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell. 2000; 6: 13551364. DOI: 10.1016/S1097-2765(00)00133-7
  12. Yamamoto, K, Sato, T, Matsui, T, Sato, M, Okada, T, et al. Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. Dev Cell. 2007; 13: 365376. DOI: 10.1016/j.devcel.2007.07.018
  13. Harding, HP, Zeng, H, Zhang, Y, Jungries, R, Chung, P, et al. Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival. Mol Cell. 2001; 7: 11531163. DOI: 10.1016/S1097-2765(01)00264-7
  14. Iwawaki, T, Akai, R and Kohno, K. IRE1α Disruption Causes Histological Abnormality of Exocrine Tissues, Increase of Blood Glucose Level, and Decrease of Serum Immunoglobulin Level. PLoS One. 2010; 5. DOI: 10.1371/journal.pone.0013052
  15. Hassler, JR, Scheuner, DL, Wang, S, Han, J, Kodali, VK, et al. The IRE1alpha/XBP1s Pathway Is Essential for the Glucose Response and Protection of beta Cells. PLoS Biol. 2015; 13: e1002277. DOI: 10.1371/journal.pbio.1002277
  16. Ozcan, U, Cao, Q, Yilmaz, E, Lee, AH, Iwakoshi, NN, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004; 306: 457461. DOI: 10.1126/science.1103160
  17. Seo, J, Fortuno, ES, 3rd, Suh, JM, Stenesen, D, Tang, W, et al. Atf4 regulates obesity, glucose homeostasis, and energy expenditure. Diabetes. 2009; 58: 25652573. DOI: 10.2337/db09-0335
  18. Russell, RC, Fang, C and Guan, KL. An emerging role for TOR signaling in mammalian tissue and stem cell physiology. Development. 2011; 138: 33433356. DOI: 10.1242/dev.058230
  19. Zoncu, R, Efeyan, A and Sabatini, DM. 2011 mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011; 12: 2135. DOI: 10.1038/nrm3025
  20. Polak, P and Hall, MN. mTOR and the control of whole body metabolism. Curr Opin Cell Biol. 2009; 21: 209218. DOI: 10.1016/j.ceb.2009.01.024
  21. Sarbassov, DD, Ali, SM, Kim, DH, Guertin, DA, Latek, RR, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004; 14: 12961302. DOI: 10.1016/j.cub.2004.06.054
  22. Appenzeller-Herzog, C and Hall, MN. Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling. Trends Cell Biol. 2012; 22: 274282. DOI: 10.1016/j.tcb.2012.02.006
  23. Qin, L, Wang, Z, Tao, L and Wang, Y. ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy. 2010; 6: 239247. DOI: 10.4161/auto.6.2.11062
  24. Kato, H, Nakajima, S, Saito, Y, Takahashi, S, Katoh, R, et al. mTORC1 serves ER stress-triggered apoptosis via selective activation of the IRE1-JNK pathway. Cell Death Differ. 2012; 19: 310320. DOI: 10.1038/cdd.2011.98
  25. King, FW, Fong, S, Griffin, C, Shoemaker, M, Staub, R, et al. Timosaponin AIII is preferentially cytotoxic to tumor cells through inhibition of mTOR and induction of ER stress. PLoS One. 2009; 4: e7283. DOI: 10.1371/journal.pone.0007283
  26. Kapuy, O, Vinod, PK and Banhegyi, G. mTOR inhibition increases cell viability via autophagy induction during endoplasmic reticulum stress – An experimental and modeling study. FEBS Open Bio. 2014; 4: 704713. DOI: 10.1016/j.fob.2014.07.006
  27. Yanagawa, S, Lee, JS and Ishimoto, A. Identification and characterization of a novel line of Drosophila Schneider S2 cells that respond to wingless signaling. J Biol Chem. 1998; 273: 3235332359. DOI: 10.1074/jbc.273.48.32353
  28. Plongthongkum, N, Kullawong, N, Panyim, S and Tirasophon, W. Ire1 regulated XBP1 mRNA splicing is essential for the unfolded protein response (UPR) in Drosophila melanogaster. Biochem Biophys Res Commun. 2007; 354: 789794. DOI: 10.1016/j.bbrc.2007.01.056
  29. Um, SH, Frigerio, F, Watanabe, M, Picard, F, Joaquin, M, et al. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature. 2004; 431: 200205. DOI: 10.1038/nature02866
  30. Haruta, T, Uno, T, Kawahara, J, Takano, A, Egawa, K, et al. A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol Endocrinol. 2000; 14: 783794. DOI: 10.1210/mend.14.6.0446
  31. Manning, BD. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol. 2004; 167: 399403. DOI: 10.1083/jcb.200408161
  32. Sanchez-Alvarez, M, Finger, F, Arias-Garcia, Mdel, M, Bousgouni, V, Pascual-Vargas, P, et al. Signaling networks converge on TORC1-SREBP activity to promote endoplasmic reticulum homeostasis. PLoS One. 2014; 9: e101164. DOI: 10.1371/journal.pone.0101164
  33. Yamazaki, H, Hiramatsu, N, Hayakawa, K, Tagawa, Y, Okamura, M, et al. Activation of the Akt-NF-kappaB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response. J Immunol. 2009; 183: 14801487. DOI: 10.4049/jimmunol.0900017
  34. Ozcan, U, Ozcan, L, Yilmaz, E, Duvel, K, Sahin, M, et al. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell. 2008; 29: 541551. DOI: 10.1016/j.molcel.2007.12.023
  35. Yin, J, Gu, L, Wang, Y, Fan, N, Ma, Y, et al. Rapamycin improves palmitate-induced ER stress/NF kappa B pathways associated with stimulating autophagy in adipocytes. Mediators Inflamm. 2015; 2015. DOI: 10.1155/2015/272313
  36. Haze, K, Yoshida, H, Yanagi, H, Yura, T and Mori, K. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell. 1999; 10: 37873799. DOI: 10.1091/mbc.10.11.3787
  37. Wu, J, Rutkowski, DT, Dubois, M, Swathirajan, J, Saunders, T, et al. ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Dev Cell. 2007; 13: 351364. DOI: 10.1016/j.devcel.2007.07.005
  38. Maruyama, R, Kamoshida, Y, Shimizu, M, Inoue, J and Sato, R. ATF6alpha stimulates cholesterogenic gene expression and de novo cholesterol synthesis. Biosci Biotechnol Biochem. 2013; 77: 17341738. DOI: 10.1271/bbb.130295
  39. Zeng, L, Lu, M, Mori, K, Luo, S, Lee, AS, et al. ATF6 modulates SREBP2-mediated lipogenesis. Embo j. 2004; 23: 950958. DOI: 10.1038/sj.emboj.7600106
  40. Usui, M, Yamaguchi, S, Tanji, Y, Tominaga, R, Ishigaki, Y, et al. Atf6alpha-null mice are glucose intolerant due to pancreatic beta-cell failure on a high-fat diet but partially resistant to diet-induced insulin resistance. Metabolism. 2012; 61: 11181128. DOI: 10.1016/j.metabol.2012.01.004
  41. Morrisett, JD, Abdel-Fattah, G, Hoogeveen, R, Mitchell, E, Ballantyne, CM, et al. Effects of sirolimus on plasma lipids, lipoprotein levels, and fatty acid metabolism in renal transplant patients. J Lipid Res. 2002; 43: 11701180.
  42. Ma, XM and Blenis, J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol. 2009; 10: 307318. DOI: 10.1038/nrm2672
  43. Hay, N and Sonenberg, N. Upstream and downstream of mTOR. Genes Dev. 2004; 18: 19261945. DOI: 10.1101/gad.1212704
  44. Nakajima, S, Hiramatsu, N, Hayakawa, K, Saito, Y, Kato, H, et al. Selective abrogation of BiP/GRP78 blunts activation of NF-kappaB through the ATF6 branch of the UPR: involvement of C/EBPbeta and mTOR-dependent dephosphorylation of Akt. Mol Cell Biol. 2011; 31: 17101718. DOI: 10.1128/MCB.00939-10
  45. Schewe, DM and Aguirre-Ghiso, JA. ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo. Proc Natl Acad Sci. 2008; 105: 1051910524. U S A. DOI: 10.1073/pnas.0800939105
  46. Okuhashi, Y, Itoh, M, Nara, N and Tohda, S. NOTCH knockdown affects the proliferation and mTOR signaling of leukemia cells. Anticancer Res. 2013; 33: 42934298.
  47. Inoki, K, Li, Y, Zhu, T, Wu, J and Guan, KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002; 4: 648657. DOI: 10.1038/ncb839
Language: English
Page range: 1 - 1
Submitted on: Feb 24, 2017
Accepted on: Jan 26, 2018
Published on: Apr 23, 2018
Published by: Danny N. Dhanasekaran
In partnership with: Paradigm Publishing Services

© 2018 Dylan Allen, Jin Seo, published by Danny N. Dhanasekaran
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 13 (2018): Issue 1