Constitutive mTORC1 activation by a herpesvirus Akt surrogate stimulates mRNA translation and viral replication

Genes and Development

Volumn 24, Issue 23, 2010, Pages 2627-2639

  Chuluunbaatar, Uyanga ^a   Roller, Richard ^b   Feldman, Morris E ^c,d   Brown, Stuart ^a   Shokat, Kevan M ^c,d   Mohr, Ian ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF IOWA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Akt signaling; Herpesvirus replication; mTOR activation; Translational control; Viral kinase

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MESSENGER RNA; PROTEIN KINASE B; PROTEIN KINASE US3; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR FKHR; TUBERIN; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; ENZYME SPECIFICITY; ENZYME SUBSTRATE; GENETIC TRANSFECTION; HERPES SIMPLEX VIRUS 1; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; NEGATIVE FEEDBACK; NONHUMAN; PRIORITY JOURNAL; PROTEIN SYNTHESIS; SEQUENCE HOMOLOGY; TRANSLATION REGULATION; VIRUS REPLICATION; WESTERN BLOTTING;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; CELL LINE; CELL LINE, TUMOR; ENZYME ACTIVATION; EUKARYOTIC INITIATION FACTOR-4F; GENE EXPRESSION REGULATION, VIRAL; HEK293 CELLS; HERPES SIMPLEX; HERPESVIRUS 1, HUMAN; HUMANS; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RNA, MESSENGER; RNA, VIRAL; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEINS; VIRAL PROTEINS; VIRUS REPLICATION;

HERPESVIRIDAE; HUMAN HERPESVIRUS 1;

EID: 78649857803     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.1978310     Document Type: Article

References (49)

1. Allen JJ, Li M, Brinkworth CS, Paulson JL, Wang D, Hübner A, Chou WH, Davis RJ, Burlingame AL, Messing RO, et al. 2007. A semisynthetic epitope for kinase substrates. Nat Methods 4: 511-516.
2. Arias C, Walsh D, Harbell J, Wilson AC, Mohr I. 2009. Activation of host translational control pathways by a viral developmental switch. PLoS Pathog 5: e1000334. doi: 10.1371/ journal.ppat.1000334.
3. Benetti L, Roizman B. 2004. Herpes simplex virus protein kinase US3 activates and functionally overlaps protein kinase A to block apoptosis. Proc Natl Acad Sci 101: 9411-9416.
4. Benetti L, Roizman B. 2006. Protein kinase B/Akt is present in activated form throughout the entire replicative cycle of DU(S)3 mutant virus but only at early times after infection with wild-type herpes simplex virus 1. J Virol 80: 3341-3348.
5. Biondi RM, Nebreda AR. 2003. Signaling specificity of ser/thr protein kinases through docking-site mediated interactions. Biochem J 372: 1-13.
6. Braunstein S, Badura ML, Xi Q, Formenti SC, Schneider RJ. 2009. Regulation of protein synthesis by ionizing radiation. Mol Cell Biol 29: 5645-5656.
7. Buchkovich NJ, Yu Y, Zampieri CA, Alwine JC. 2008. The TORrid affairs of viruses: Effects of mammalian DNA viruses on the PI3K-Akt-mTOR signaling pathway. Nat Rev Microbiol 6: 266-275.
8. Calleja V, Laguerre M, Parker PJ, Larijani B. 2009. Role of a novel PH-kinase domain interface in PKB/Akt regulation: Structural mechanism for allosteric inhibition. PLoS Biol 7: e17. doi: 10.1371/journal.pbio.1000017.
9. Dibble CC, Asara JM, Manning BD. 2009. Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol 29: 5657-5670.
10. Dobrikova E, Shveygert M, Walters R, Gromeier M. 2009. Herpes simplex virus proteins ICP27 and UL47 associate with polyadenylate-binding protein and control its sub-cellular distribution. J Virol 84: 270-279.
11. Elia A, Constantinou C, Clemens MJ. 2008. Effects of protein phosphorylation on ubiquitination and stability of the translational inhibitor protein 4E-BP1. Oncogene 27: 811-822.
12. Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D, Shokat KM. 2009. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 7: e38. doi: 10.1371/journal.pbio.1000038.
13. Felsenstein J. 1985. Confidence limits on phylogenies: An approach using the bootstrap. Evolution 39: 783-791.
14. Gingras AC, Gygi SP, Raught B, Polakiewicz RD, Abraham RT, Hoekstra MF, Aebersold R, Sonenberg N. 1999. Regulation of 4E-BP1 phosphorylation: A novel two-step mechanism. GenesDev 13: 1422-1437.
15. Harrington LS, Findlay GM, Lamb RF. 2005. Restraining PI3K: mTOR signaling goes back to the membrane. Trends Biochem Sci 30: 35-42.
16. Kato A, Yamamoto M, Ohno T, Kodaira H, Nishiyama Y, Kawaguchi Y. 2005. Identification of proteins phosphorylated directly by the Us3 protein kinase encoded by herpes simplex virus 1. J Virol 79: 9325-9331.
17. Kato A, Yamamoto M, Ohno T, Tanaka M, Sata T, Nishiyama Y, Kawaguchi Y. 2006. Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31. J Virol 80: 1476-1486.
18. Kudchodkar SB, Yu Y, Maguire TG, Alwine JC. 2004. Human cytomegalovirus infection induces rapamycin-insensitive phosphorylation of downstream effectors of mTOR kinase. J Virol 78: 11030-11039.
19. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, et al. 2007. ClustalW and ClustalX version 2. Bioinformatics 23: 2947-2948.
20. Leach N, Bjerke SL, Christensen DK, Bouchard JM, Mou F, Park R, Baines J, Haraguchi T, Roller RJ. 2007. Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3. J Virol 81: 10792-10803.
21. Leader DP, Deana AD, Marchiori F, Purves FC, Pinna LA. 1991. Further definition of the substrate specificity of the a-herpesvirus protein kinase and comparison with protein kinases A and C. Biochim Biophys Acta 1091: 426-431.
22. Lu Z, Hu X, Li Y, Zheng L, Zhou Y, Jiang H, Ning T, Basang Z, Zhang C, Ke Y. 2004. Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin. J Biol Chem 279: 35664-35670.
23. Ma XM, Blenis J. 2009. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10: 307-318.
24. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC. 2002. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell 10: 151-162.
25. Meignier B, Longnecker R, Mavromara-Nazos P, Sears AE, Roizman B. 1988. Virulence of and establishment of latency by genetically engineered deletion mutants of herpes simplex virus 1. Virology 162: 251-254.
26. Mohr IJ, Pe'ery T, Mathews MB. 2007. Protein synthesis and translational control during viral infection. In Translational control in biology and medicine (ed. MB Mathews, N Sonenberg, JWB Hershey), pp. 545-595. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
27. Moorman NJ, Shenk T. 2010. Rapamycin-resistant mTORC1 kinase activity is required for herpesvirus replication. J Virol 84: 5260-5269.
28. Moorman NJ, Cristea IM, Terhune SS, Rout MP, Chait BT, Shenk T. 2008. Human cytomegalovirus protein UL38 inhibits host cell stress responses by antagonizing the tuberous sclerosis protein complex. Cell Host Microbe 3: 253-262.
29. Mou F, Forest T, Baines JD. 2007. US3 of herpes simplex virus type 1 encodes a promiscuous protein kinase that phosphorylates and alters localization of lamin A/C in infected cells. J Virol 81: 6459-6470.
30. Munger J, Roizman B. 2001. The US3 protein kinase of herpes simplex virus 1 mediates the posttranslational modification of BAD and prevents BAD-induced programmed cell death in the absence of other viral proteins. Proc Natl Acad Sci 98: 10410-10415.
31. Nei M, Kumar S. 2000. Molecular evolution and phylogenetics. Oxford University Press, New York.
32. Nishiyama Y, Yamada Y, Kurachi R, Daikoku T. 1992. Construction of a US3 lacZ insertion mutant of herpes simplex virus type 2 and characterization of its phenotype in vitro and in vivo. Virology 190: 256-268.
33. Ogg PD, McDonell PJ, Ryckman BJ, Knudson CM, Roller RJ. 2004. The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by over-expression of a variety of Bcl-2 family members. Virology 319: 212-224.
34. Pawson T, Nash P. 2000. Protein-protein interactions define specificity in signal transduction. GenesDev 14: 1027-1047.
35. Poon AP, Gu H, Roizman B. 2006. ICP0 and the US3 protein kinase of herpes simplex virus 1 independently block histone deacetylation to enable gene expression. Proc Natl Acad Sci 103: 9993-9998.
36. Remenyi A, Good MC, Lim WA. 2006. Docking interactions in protein kinase and phosphatase networks. Curr Opin Struct Biol 16: 676-685.
37. Roizman B, Knipe DM, Whitley R. 2007. Herpes simplex viruses. In Fields' virology, 5th ed. (ed. DM Knipe, PM Howley), pp. 2501-2602. Lippincott, Williams & Wilkins, Philadelphia, PA.
38. Ryckman BJ, Roller RJ. 2004. Herpes simplex virus type 1 primary envelopment: UL34 protein modification and the US3-UL34 catalytic relationship. J Virol 78: 399-412.
39. Rzhetsky A, Nei M. 1992. A simple method for estimating and testing minimum evolution trees. Mol Biol Evol 9: 945-967.
40. Sagou K, Imai T, Sagara H, Uema M, Kawaguchi Y. 2009. Regulation of the catalytic activity of herpes simplex virus 1 protein kinase Us3 by autophosphorylation and its role in pathogenesis. J Virol 83: 5773-5783.
41. Saitou N, Nei M. 1987. The neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol Biol Evol 4: 406-425.
42. Seghal SN. 2003. Sirolimus: Its discovery, biological properties and mechanism of action. Transplant Proc 35: S7-S14. doi: 10.1016/S0041-1345(03) 00211-2.
43. Sodhi A, Chaisuparat R, Hu J, Ramsdell AK, Manning BD, Sausville EA, Sawai ET, Molinolo A, Gutkind JS, Montaner S. 2006. The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. Cancer Cell 10: 133-143.
44. Sonenberg N, Hinnebusch AG. 2009. Regulation of translation initiation in eukaryotes: Mechanisms and biological targets. Cell 136: 731-745.
45. Tamura K, Dudley J, Nei M, Kumar S. 2007. MEGA4: Molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24: 1596-1599.
46. Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS. 2009. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 284: 8023-8032.
47. Walsh D, Mohr I. 2004. Phosphorylation of eIF4E by Mnk-1 enhances HSV-1 translation and replication in quiescent cells. Genes Dev 18: 660-672.
48. Walsh D, Mohr I. 2006. Assembly of an active translation initiation factor complex by a viral protein. Genes Dev 20: 461-472.
49. Walsh D, Perez C, Notary J, Mohr I. 2005. Regulation of the translation initiation factor eIF4F by multiple mechanisms in human cytomegalovirus-infected cells. J Virol 79: 8057-8064.