Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes theintegrated stress response

eLife

Volumn 2015, Issue 4, 2015, Pages

  Sidrauski, Carmela ^a,b   Tsai, Jordan C ^a,b   Kampmann, Martin ^b   Hearn, Brian R ^b   Vedantham, Punitha ^b   Jaishankar, Priyadarshini ^b   Sokabe, Masaaki ^c   Mendez, Aaron S ^a,b   Newton, Billy W ^d   Tang, Edward L ^d,e   Verschueren, Erik ^d   Johnson, Jeffrey R ^d,e   Krogan, Nevan J ^d,e   Fraser, Christopher S ^c   Weissman, Jonathan S ^b   Renslo, Adam R ^b   Walter, Peter ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e GLADSTONE INSTITUTES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EUKARYOTIC TRANSLATION INITIATION FACTOR 2B; INITIATION FACTOR; SHORT HAIRPIN RNA; UNCLASSIFIED DRUG; 2-(4-CHLOROPHENOXY)-N-(4-(2-(4-CHLOROPHENOXY)ACETAMIDO)CYCLOHEXYL)ACETAMIDE; ACETAMIDE DERIVATIVE; BACTERIAL PROTEIN; CYCLOHEXYLAMINE DERIVATIVE; GUANINE NUCLEOTIDE EXCHANGE FACTOR; NEUROPROTECTIVE AGENT; NOOTROPIC AGENT; PHOTOPROTEIN; PROTEIN BINDING; PROTEIN SUBUNIT; SMALL INTERFERING RNA; THAPSIGARGIN; YELLOW FLUORESCENT PROTEIN, BACTERIA;

ARTICLE; CELLULAR EXTRACT THERMAL SHIFT ASSAY; COGNITION; DEGENERATIVE DISEASE; DIMERIZATION; ENZYME ACTIVITY; GDP DISSOCIATION ASSAY; GENE ACTIVATION; GENE SILENCING; GENETIC ANALYSIS; HUMAN; HUMAN CELL; MASS SPECTROMETRY; PROTEIN ANALYSIS; PROTEIN PHOSPHORYLATION; QUANTITATIVE ASSAY; SIGNAL TRANSDUCTION; STRESS; STRUCTURE ACTIVITY RELATION; TRANSLATION INITIATION; WESTERN BLOTTING; ANTAGONISTS AND INHIBITORS; BINDING SITE; CHEMISTRY; DRUG EFFECTS; ENDOPLASMIC RETICULUM STRESS; GENE EXPRESSION; GENETICS; HEK293 CELL LINE; HELA CELL LINE; HIGH THROUGHPUT SCREENING; K-562 CELL LINE; METABOLISM; PHOSPHORYLATION; PROTEIN MULTIMERIZATION; PROTEIN SUBUNIT; REPORTER GENE; SYNTHESIS;

RODENTIA;

ACETAMIDES; BACTERIAL PROTEINS; BINDING SITES; CYCLOHEXYLAMINES; ENDOPLASMIC RETICULUM STRESS; EUKARYOTIC INITIATION FACTOR-2B; GENE EXPRESSION; GENES, REPORTER; HEK293 CELLS; HELA CELLS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; K562 CELLS; LUMINESCENT PROTEINS; NEUROPROTECTIVE AGENTS; NOOTROPIC AGENTS; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN SUBUNITS; RNA, SMALL INTERFERING; STRUCTURE-ACTIVITY RELATIONSHIP; THAPSIGARGIN;

EID: 84928141313     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.07314     Document Type: Article

References (54)

1. Baleriola, J., Walker, C.A., Jean, Y.Y., Crary, J.F., Troy, C.M., Nagy, P.L., and Hengst, U. (2014). Axonally Synthesized ATF4 Transmits a Neurodegenerative Signal across Brain Regions. Cell 158, 1159-1172.
2. Bassik, M.C., Kampmann, M., Lebbink, R.J., Wang, S., Hein, M.Y., Poser, I., Weibezahn, J., Horlbeck, M.A., Chen, S., Mann, M., et al. (2013). A systematic mammalian genetic interaction map reveals pathways underlying ricin susceptibility. Cell 152, 909-922.
3. Bogorad, A.M., Xia, B., Sandor, D.G., Mamonov, A.B., Cafarella, T.R., Jehle, S., Vajda, S., Kozakov, D., and Marintchev, A. (2014). Insights into the architecture of the eIF2Ba/p/5 regulatory subcomplex. Biochemistry 53, 3432-3445.
4. Borck, G., Shin, B.-S., Stiller, B., Mimouni-Bloch, A., Thiele, H., Kim, J.-R., Thakur, M., Skinner, C., Aschenbach, L., Smirin-Yosef, P., et al. (2012). eIF2y Mutation that Disrupts eIF2 Complex Integrity Links Intellectual Disability to Impaired Translation Initiation. Molecular Cell 48, 641-646.
5. Chen, A., Muzzio, I.A., Malleret, G., Bartsch, D., Verbitsky, M., Pavlidis, P., Yonan, A.L., Vronskaya, S., Grody, M.B., and Cepeda, I. (2003). Inducible Enhancement of Memory Storage and Synaptic Plasticity in Transgenic Mice Expressing an Inhibitor of ATF4 (CREB-2) and C/EBP Proteins. Neuron 39, 655-669.
6. Cox, J., and Mann, M. (2008). MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nature Biotechnology. 26, 1367-1372.
7. Dev, K., Qiu, H., Dong, J., Zhang, F., Barthlme, D., and Hinnebusch, A.G. (2010). The /Gcd7 Subunit of Eukaryotic Translation Initiation Factor 2B (eIF2B), a Guanine Nucleotide Exchange Factor, Is Crucial for Binding eIF2 In Vivo. Molecular and Cellular Biology 30, 5218-5233.
8. Di Prisco, G.V., Huang, W., Buffington, S.A., Hsu, C.-C., Bonnen, P.E., Placzek, A.N., Sidrauski, C., Krnjevic, K., Kaufman, R.J., Walter, P., et al. (2014). Translational control of mGluR-dependent long-term depression and object-place learning by eIF2a. Nature Neuroscience 17, 1073-1082.
9. Fogli, A., and Boespflug-Tanguy, O. (2006). The large spectrum of eIF2B-related diseases. Biochem. Soc. Trans. 34, 22-29.
10. Fraser, C.S., Berry, K.E., Hershey, J.W.B., and Doudna, J.A. (2007). eIF3j is located in the decoding center of the human 40S ribosomal subunit. Molecular Cell 26, 811-819.
11. Gordiyenko, Y., Schmidt, C., Jennings, M.D., Matak-Vinkovic, D., Pavitt, G.D. and Robinson, C.V. (2014). eIF2B is a decameric guanine nucleotide exchange factor with a y2s2 tetrameric core. Nature Communications 5, 1-12.
12. Harding, H.P., Novoa, I., Zhang, Y., Zeng, H., Wek, R., Schapira, M., and Ron, D. (2000). Regulated translation initiation controls stress-induced gene expression in mammalian cells. Molecular Cell 6, 1099-1108.
13. Harding, H.P., Zhang, Y., Zeng, H., Novoa, I., Lu, P.D., Calfon, M., Sadri, N., Yun, C., Popko, B., Paules, R., et al. (2003). An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress. Molecular Cell 11, 619-633.
14. Hinnebusch, A.G., and Lorsch, J.R. (2012). The Mechanism of Eukaryotic Translation Initiation: New Insights and Challenges. Cold Spring Harbor Perspectives in Biology 4, a011544-a011544.
15. Jennings, M.D., Zhou, Y., Mohammad-Qureshi, S.S., Bennett, D. and Pavitt, G.D. (2013). eIF2B promotes eIF5 dissociation from eIF2*GDP to facilitate guanine nucleotide exchange for translation initiation. Genes & Development 27, 2696-2707.
16. Jennings, M.D., and Pavitt, G.D. (2014). A new function and complexity for protein translation initiation factor eIF2B. Cell Cycle 13, 2660-2665.
17. Jennings, M.D., and Pavitt, G.D. (2015). eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation. Nature 465, 378-381.
18. Julien, O., Kampmann, M., Bassik, M.C., Zorn, J.A., Venditto, V.J., Shimbo, K., Agard, N.J., Shimada, K., Rheingold, A.L., Stockwell, B.R., et al. (2014). Unraveling the mechanism of cell death induced by chemical fibrils. Nature Chemical Biology 10, 969-976.
19. Kampmann, M., Bassik, M.C., and Weissman, J.S. (2013). Integrated platform for genome-wide screening and construction of high-density genetic interaction maps in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 110, E2317-E2326.
20. Kampmann, M., Bassik, M.C., and Weissman, J.S. (2014). Functional genomics platform for pooled screening and generation of mammalian genetic interaction maps. Nature Protocols 9, 1825-1847.
21. Kim, H.-J., Raphael, A.R., LaDow, E.S., McGurk, L., Weber, R.A., Trojanowski, J.Q., Lee, V.M.-Y., Finkbeiner, S., Gitler, A.D., and Bonini, N.M. (2013). Therapeutic modulation of eIF2a phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nature Genetics 46, 152-160.
22. Kimball, S.R., Fabian, J.R., Pavitt, G.D., Hinnebusch, A.G., and Jefferson, L.S. (1998). Regulation of guanine nucleotide exchange through phosphorylation of eukaryotic initiation factor eIF2alpha. Role of the alpha- and delta-subunits of eiF2b. Journal of Biological Chemistry 273, 12841-12845.
23. Krishnamoorthy, T., Pavitt, G.D., Zhang, F., Dever, T.E., and Hinnebusch, A.G. (2001). Tight Binding of the Phosphorylated Subunit of Initiation Factor 2 (eIF2) to the Regulatory Subunits of Guanine Nucleotide Exchange Factor eIF2B Is Required for Inhibition of Translation Initiation. Molecular and Cellular Biology 21, 5018-5030.
24. Lee, Y.Y., Cevallos, R.C., and Jan, E. (2009). An Upstream Open Reading Frame Regulates Translation of GADD34 during Cellular Stresses That Induce eIF2 Phosphorylation. Journal of Biological Chemistry 284, 6661-6673.
25. Leegwater, P.A., Vermeulen, G., Konst, A.A., Naidu, S., Mulders, J., Visser, A., Kersbergen, P., Mobach, D., Fonds, D., van Berkel, C.G., et al. (2001). Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter. Nature Genetics 29, 383-388.
26. Leitman, J., Barak, B., Benyair, R., Shenkman, M., Ashery, U., Hartl, F.U., and Lederkremer, G.Z. (2014). ER Stress-Induced eIF2-alpha Phosphorylation Underlies Sensitivity of Striatal Neurons to Pathogenic Huntingtin. PLoS ONE 9, e90803.
27. Li, W., Wang, X., van der Knaap, M.S., and Proud, C.G. (2004). Mutations linked to Leukoencephalopathy with Vanishing White Matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways. Molecular and Cellular Biology 24, 3295-3306.
28. Lu, P.D. (2004). Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response. The Journal of Cell Biology 167, 27-33.
29. Ma, T., Trinh, M.A., Wexler, A.J., Bourbon, C., Gatti, E., Pierre, P., Cavener, D.R., and Klann, E. (2013). Suppression of eIF2a kinases alleviates Alzheimer's disease-related plasticity and memory deficits. Nature Neuroscience 16, 1299-1305.
30. Martin, L., Kimball, S.R., and Gardner, L.B. (2010). Regulation of the Unfolded Protein Response by eIF2B Isoforms. Journal of Biological Chemistry 285, 31944-31953.
31. Matheny, C.J., Wei, M.C., Bassik, M.C., Donnelly, A.J., Kampmann, M., Iwasaki, M., Piloto, O., Solow-Cordero, D.E., Bouley, D.M., Rau, R., et al. (2013). Next-generation NAMPT nhibitors identified by sequential high-throughput phenotypic chemical and functional genomic screens. Chemistry & Biology 20, 1352-1363.
32. Molina, D.M., Jafari, R., Ignatushchenko, M., Seki, T., Larsson, E.A., Dan, C., Sreekumar, L., Cao, Y., and Nordlund, P. (2013). Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay. Science 341, 84-87.
33. Moreno, J.A., Halliday, M., Molloy, C., Radford, H., Verity, N., Axten, J.M., Ortori, C.A., Willis, A.E., Fischer, P.M., Barrett, D.A., et al. (2013). Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice. Science Translational Medicine 5, 206ra138.
34. Moreno, J.A., Radford, H., Peretti, D., Steinert, J.R., Verity, N., Martin, M.G., Halliday, M., Morgan, J., Dinsdale, D., Ortori, C.A., et al. (2012). Sustained translational repression by eIF2a- P mediates prion neurodegeneration. Nature 485, 507-511.
35. Nadif Kasri, N., Nakano-Kobayashi, A., and Van Aelst, L. (2011). Rapid Synthesis of the X- Linked Mental Retardation Protein OPHN1 Mediates mGluR-Dependent LTD through Interaction with the Endocytic Machinery. Neuron 72, 300-315.
36. Novoa, I., Zeng, H., Harding, H.P., and Ron, D. (2001). Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. The Journal of Cell Biology 153, 1011-1022.
37. Oldfield, S., and Proud, C.G. (1992). Purification, phosphorylation and control of the guanine- nucleotide-exchange factor from rabbit reticulocyte lysates. Eur. J. Biochem. 208, 73-81.
38. Palam, L.R., Baird, T.D., and Wek, R.C. (2011). Phosphorylation of eIF2 facilitates ribosomal bypass of an inhibitory upstream ORF to enhance CHOP translation. J. Biol. Chem. 286, 1093910949.
39. Pavitt, G.D., Yang, W., and Hinnebusch, A.G. (1997). Homologous segments in three subunits of the guanine nucleotide exchange factor eIF2B mediate translational regulation by phosphorylation of eIF2. Molecular and Cellular Biology 17, 1298-1313.
40. Ramage, H.R., Kumar, G.R., Verschueren, E., Johnson, J.R., Dollen, Von.J., Johnson, T., Newton, B., Shah, P., Horner, J., Krogan, N.J., et al. (2015). A combined proteomics/genomics approach links hepatitis C virus infection with nonsense-mediated mRNA decay. Molecular Cell 57, 329-340.
41. Roy, B., Vaughn, J. N., Kim B-H., Zhou, F., Gilchrist M.A. and Von Armin, A.G., (2010), The h subunit of eIF3 promotes reinitiation competence during translation of mRNAs harboring upstream open reading frames. RNA 16, 748-761.
42. Sidrauski, C., Acosta-Alvear, D., Khoutorsky, A., Vedantham, P., Hearn, B.R., Li, H., Gamache, K., Gallagher, C.M., Ang, K.K.-H., Wilson, C., et al. (2013). Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2, e00498.
43. Sidrauski, C., McGeachy, A.M., Ingolia, N.T., and Walter, P. (2015). The small molecule ISRIB reverses the effects of eIF2a phosphorylation on translation and stress granule assembly. Elife 4, e05033.
44. Szamecz, B., Rutkai E., Cuchalova L., Munzarova, V., Herrmannova, A., Nielsen, K.H., Laxminarayana, B., Hinnebusch, A. G. and Valasek, L. (2008). eIF3a cooperates with sequences 5' of uORF1 to promote resumption of scanning by post-termination ribosomes for reinitiation on GCN4. Genes and Development 22, 2414-2525.
45. Sokabe, M., Fraser, C.S., and Hershey, J.W.B. (2012). The human translation initiation multifactor complex promotes methionyl-tRNAi binding to the 40S ribosomal subunit. Nucleic Acids Research 40, 905-913.
46. Vattem, K.M., and Wek, R.C. (2004). Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proceedings of the National Academy of Sciences 101, 11269-11274.
47. Ventura, A., Meissner, A., Dillon, C.P., McManus, M., Sharp, P.A., Van Parijs, L., Jaenisch, R., and Jacks, T. (2004). Cre-lox-regulated conditional RNA interference from transgenes. Proceedings of the National Academy of Sciences 101, 10380-10385.
48. Wang, G., Han, T., Nijhawan, D., Theodoropoulos, P., Naidoo, J., Yadavalli, S., Mirzaei, H., Pieper, A.A., Ready, J.M., and McKnight, S.L. (2014). P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage. Cell 158, 1324-1334.
49. Wek, R.C., Jiang, H.-Y., and Anthony, T.G. (2006). Coping with stress: eIF2 kinases and translational control. Biochem. Soc. Trans. 34, 7-11.
50. Williams, D.D. (2001). Characterization of the Mammalian Initiation Factor eIF2B Complex as a GDP Dissociation Stimulator Protein. Journal of Biological Chemistry 276, 24697-24703.
51. Wiseman, R.L., Zhang, Y., Lee, K.P.K., Harding, H.P., Haynes, C.M., Price, J., Sicheri, F., and Ron, D. (2010). Flavonol activation defines an unanticipated ligand-binding site in the kinase- RNase domain of IRE1. Molecular Cell 38, 291-304.
52. Wortham, N.C., Martinez, M., Gordiyenko, Y., Robinson, C.V., and Proud, C.G. (2014).Analysis of the subunit organization of the eIF2B complex reveals new insights into its structure and regulation. The FASEB Journal 28, 2225-2237.
53. Ye, J., Kumanova, M., Hart, L.S., Sloane, K., Zhang, H., De Panis, D.N., Bobrovnikova-Marjon, E., Diehl, J.A., Ron, D., and Koumenis, C. (2010). The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. The EMBO Journal 29, 2082-2096.
54. Zorn, J.A., and Wells, J.A. (2010). Turning enzymes ON with small molecules. Nature Chemical Biology 6, 179-188.