Viral and Cellular Proteins Containing FGDF Motifs Bind G3BP to Block Stress Granule Formation

English version České info

Stress granules (SGs) are dynamic aggregates of proteins and translationally silenced mRNA that are formed in cells upon various stress conditions, such as virus infection. SGs are thought to be antiviral, and many viruses have hence evolved countermeasures to prevent their formation, often targeting the essential SG protein G3BP. Here, we show that several otherwise unrelated viral and cellular proteins all bind G3BP with the sequence motif FGDF, and thereby repress SG formation: the non-structural protein 3 (nsP3) of the Old World alphavirus Semliki Forest virus (a close relative of the emerging, highly pathogenic Chikungunya virus); the protein ICP8 of herpes simplex virus; and in addition, the cellular protein USP10 (an SG component and protein deubiquitinase that stabilises e.g. the tumor suppressor p53). In this work, we also present and validate a model of the three-dimensional structure of G3BP bound to an FGDF-containing peptide. The FGDF-mediated G3BP binding represents an attractive target for therapeutic interventions against a range of diverse viral infections, and may also regulate the p53-stabilising function of USP10 in cancers.

Vyšlo v časopise: Viral and Cellular Proteins Containing FGDF Motifs Bind G3BP to Block Stress Granule Formation. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004659
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004659

Souhrn

Zdroje

1. Matsuki H, Takahashi M, Higuchi M, Makokha GN, Oie M, et al. (2013) Both G3BP1 and G3BP2 contribute to stress granule formation. Genes Cells 18: 135–146. doi: 10.1111/gtc.12023 23279204

2. Tourriere H, Chebli K, Zekri L, Courselaud B, Blanchard JM, et al. (2003) The RasGAP-associated endoribonuclease G3BP assembles stress granules. J Cell Biol 160: 823–831. 12642610

3. Kedersha NL, Gupta M, Li W, Miller I, Anderson P (1999) RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. J Cell Biol 147: 1431–1442. 10613902

4. Dang Y, Kedersha N, Low WK, Romo D, Gorospe M, et al. (2006) Eukaryotic initiation factor 2alpha-independent pathway of stress granule induction by the natural product pateamine A. J Biol Chem 281: 32870–32878. 16951406

5. Suyama M, Doerks T, Braun IC, Sattler M, Izaurralde E, et al. (2000) Prediction of structural domains of TAP reveals details of its interaction with p15 and nucleoporins. EMBO Rep 1: 53–58. 11256625

6. Tourriere H, Gallouzi IE, Chebli K, Capony JP, Mouaikel J, et al. (2001) RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization. Mol Cell Biol 21: 7747–7760. 11604510

7. Solomon S, Xu Y, Wang B, David MD, Schubert P, et al. (2007) Distinct structural features of caprin-1 mediate its interaction with G3BP-1 and its induction of phosphorylation of eukaryotic translation initiation factor 2alpha, entry to cytoplasmic stress granules, and selective interaction with a subset of mRNAs. Mol Cell Biol 27: 2324–2342. 17210633

8. Soncini C, Berdo I, Draetta G (2001) Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease. Oncogene 20: 3869–3879. 11439350

9. Wehner KA, Schutz S, Sarnow P (2010) OGFOD1, a novel modulator of eukaryotic translation initiation factor 2alpha phosphorylation and the cellular response to stress. Mol Cell Biol 30: 2006–2016. doi: 10.1128/MCB.01350-09 20154146

10. Bomberger JM, Barnaby RL, Stanton BA (2009) The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of cystic fibrosis transmembrane conductance regulator in airway epithelial cells. J Biol Chem 284: 18778–18789. doi: 10.1074/jbc.M109.001685 19398555

11. Yuan J, Luo K, Zhang L, Cheville JC, Lou Z (2010) USP10 regulates p53 localization and stability by deubiquitinating p53. Cell 140: 384–396. doi: 10.1016/j.cell.2009.12.032 20096447

12. Liu J, Xia H, Kim M, Xu L, Li Y, et al. (2011) Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell 147: 223–234. doi: 10.1016/j.cell.2011.08.037 21962518

13. Lin Z, Yang H, Tan C, Li J, Liu Z, et al. (2013) USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation. Cell Rep 5: 1639–1649. doi: 10.1016/j.celrep.2013.11.029 24332849

14. Niu J, Shi Y, Xue J, Miao R, Huang S, et al. (2013) USP10 inhibits genotoxic NF-kappaB activation by MCPIP1-facilitated deubiquitination of NEMO. EMBO J 32: 3206–3219. doi: 10.1038/emboj.2013.247 24270572

15. Bomberger JM, Ely KH, Bangia N, Ye S, Green KA, et al. (2014) Pseudomonas aeruginosa Cif protein enhances the ubiquitination and proteasomal degradation of the transporter associated with antigen processing (TAP) and reduces major histocompatibility complex (MHC) class I antigen presentation. J Biol Chem 289: 152–162. doi: 10.1074/jbc.M113.459271 24247241

16. Takahashi M, Higuchi M, Matsuki H, Yoshita M, Ohsawa T, et al. (2013) Stress granules inhibit apoptosis by reducing reactive oxygen species production. Mol Cell Biol 33: 815–829. doi: 10.1128/MCB.00763-12 23230274

17. Oi N, Yuan J, Malakhova M, Luo K, Li Y, et al. (2014) Resveratrol induces apoptosis by directly targeting Ras-GTPase-activating protein SH3 domain-binding protein 1. Oncogene: doi: 10.1038/onc.2014.1194.

18. Reineke LC, Lloyd RE (2013) Diversion of stress granules and P-bodies during viral infection. Virology 436: 255–267. doi: 10.1016/j.virol.2012.11.017 23290869

19. White JP, Cardenas AM, Marissen WE, Lloyd RE (2007) Inhibition of cytoplasmic mRNA stress granule formation by a viral proteinase. Cell Host Microbe 2: 295–305. 18005751

20. Piotrowska J, Hansen SJ, Park N, Jamka K, Sarnow P, et al. (2010) Stable formation of compositionally unique stress granules in virus-infected cells. J Virol 84: 3654–3665. doi: 10.1128/JVI.01320-09 20106928

21. Katsafanas GC, Moss B (2007) Colocalization of transcription and translation within cytoplasmic poxvirus factories coordinates viral expression and subjugates host functions. Cell Host Microbe 2: 221–228. 18005740

22. Simpson-Holley M, Kedersha N, Dower K, Rubins KH, Anderson P, et al. (2011) Formation of antiviral cytoplasmic granules during orthopoxvirus infection. J Virol 85: 1581–1593. doi: 10.1128/JVI.02247-10 21147913

23. Yi Z, Fang C, Pan T, Wang J, Yang P, et al. (2006) Subproteomic study of hepatitis C virus replicon reveals Ras-GTPase-activating protein binding protein 1 as potential HCV RC component. Biochem Biophys Res Commun 350: 174–178. 16996479

24. Garaigorta U, Heim MH, Boyd B, Wieland S, Chisari FV (2012) Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress. J Virol 86: 11043–11056. 22855484

25. Cristea IM, Carroll JW, Rout MP, Rice CM, Chait BT, et al. (2006) Tracking and elucidating alphavirus-host protein interactions. J Biol Chem 281: 30269–30278. 16895903

26. Frolova E, Gorchakov R, Garmashova N, Atasheva S, Vergara LA, et al. (2006) Formation of nsP3-specific protein complexes during Sindbis virus replication. J Virol 80: 4122–4134. 16571828

27. Panas MD, Ahola T, McInerney GM (2014) The C-Terminal Repeat Domains of nsP3 from the Old World Alphaviruses Bind Directly to G3BP. J Virol 88: 5888–5893. doi: 10.1128/JVI.00439-14 24623412

28. Panas MD, Varjak M, Lulla A, Er Eng K, Merits A, et al. (2012) Sequestration of G3BP coupled with efficient translation inhibits stress granules in Semliki Forest virus infection. Mol Biol Cell 23: 4701–4712. doi: 10.1091/mbc.E12-08-0619 23087212

29. McInerney GM, Kedersha NL, Kaufman RJ, Anderson P, Liljeström P (2005) Importance of eIF2a phosphorylation and stress granule assembly in alphavirus translation regulation. Mol Biol Cell 16: 3753–3763. 15930128

30. Varjak M, Zusinaite E, Merits A (2010) Novel functions of the alphavirus nonstructural protein nsP3 C-terminal region. J Virol 84: 2352–2364. doi: 10.1128/JVI.01540-09 20015978

31. Varjak M, Saul S, Arike L, Lulla A, Peil L, et al. (2013) Magnetic fractionation and proteomic dissection of cellular organelles occupied by the late replication complexes of Semliki Forest virus. J Virol 87: 10295–10312. doi: 10.1128/JVI.01105-13 23864636

32. Scheuner D, Song B, McEwen E, Liu C, Laybutt R, et al. (2001) Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell 7: 1165–1176. 11430820

33. Vognsen T, Moller IR, Kristensen O (2013) Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup repeat specificity. PLoS ONE 8: e80947. doi: 10.1371/journal.pone.0080947 24324649

34. Taylor TJ, Knipe DM (2003) C-terminal region of herpes simplex virus ICP8 protein needed for intranuclear localization. Virology 309: 219–231. 12758170

35. Muylaert I, Tang KW, Elias P (2011) Replication and recombination of herpes simplex virus DNA. J Biol Chem 286: 15619–15624. doi: 10.1074/jbc.R111.233981 21362621

36. Reineke LC, Dougherty JD, Pierre P, Lloyd RE (2012) Large G3BP-induced granules trigger eIF2alpha phosphorylation. Mol Biol Cell 23: 3499–3510. doi: 10.1091/mbc.E12-05-0385 22833567

37. He B, Gross M, Roizman B (1997) The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci U S A 94: 843–848. 9023344

38. Dauber B, Pelletier J, Smiley JR (2011) The herpes simplex virus 1 vhs protein enhances translation of viral true late mRNAs and virus production in a cell type-dependent manner. J Virol 85: 5363–5373. doi: 10.1128/JVI.00115-11 21430045

39. Esclatine A, Taddeo B, Roizman B (2004) Herpes simplex virus 1 induces cytoplasmic accumulation of TIA-1/TIAR and both synthesis and cytoplasmic accumulation of tristetraprolin, two cellular proteins that bind and destabilize AU-rich RNAs. J Virol 78: 8582–8592. 15280467

40. Finnen RL, Pangka KR, Banfield BW (2012) Herpes simplex virus 2 infection impacts stress granule accumulation. J Virol 86: 8119–8130. doi: 10.1128/JVI.00313-12 22623775

41. Knipe DM, Spang AE (1982) Definition of a series of stages in the association of two herpesviral proteins with the cell nucleus. J Virol 43: 314–324. 6287005

42. Neuvonen M, Kazlauskas A, Martikainen M, Hinkkanen A, Ahola T, et al. (2011) SH3 domain-mediated recruitment of host cell amphiphysins by alphavirus nsP3 promotes viral RNA replication. PLoS Pathog 7: e1002383. doi: 10.1371/journal.ppat.1002383 22114558

43. Stow ND, Hammarsten O, Arbuckle MI, Elias P (1993) Inhibition of herpes simplex virus type 1 DNA replication by mutant forms of the origin-binding protein. Virology 196: 413–418. 8396795

44. Ulper L, Sarand I, Rausalu K, Merits A (2008) Construction, properties, and potential application of infectious plasmids containing Semliki Forest virus full-length cDNA with an inserted intron. J Virol Methods 148: 265–270. 18054090

45. Breakwell L, Dosenovic P, Karlsson Hedestam GB, D'Amato M, Liljeström P, et al. (2007) Semliki Forest virus nonstructural protein 2 is involved in suppression of the type I interferon response. J Virol 81: 8677–8684. 17553895

46. Eng KE, Panas MD, Murphy D, Karlsson Hedestam GB, McInerney GM (2012) Accumulation of autophagosomes in Semliki Forest virus infected cells is dependent on the expression of the viral glycoproteins. J Virol 86: 5674–5685. doi: 10.1128/JVI.06581-11 22438538

47. Liljeström P, Garoff H (1991) A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology (N Y) 9: 1356–1361. 1370252

48. Tamberg N, Lulla V, Fragkoudis R, Lulla A, Fazakerley JK, et al. (2007) Insertion of EGFP into the replicase gene of Semliki Forest virus results in a novel, genetically stable marker virus. J Gen Virol 88: 1225–1230. 17374766