Structure- and modeling-based identification of the adenovirus E4orf4 binding site in the protein phosphatase 2A B55α subunit

Journal of Biological Chemistry

Volumn 288, Issue 19, 2013, Pages 13718-13727

  Horowitz, Ben ^a,b   Sharf, Rakefet ^a   Avital Shacham, Meirav ^a   Pechkovsky, Antonina ^a   Kleinberger, Tamar ^a  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN PHOSPHATASE 2A; SUBSTRATE-BINDING SITES;

BIOCHEMISTRY;

BIOLOGY;

E4ORF4 PROTEIN; PHOSPHOPROTEIN PHOSPHATASE 2A; PHOSPHOPROTEIN PHOSPHATASE 2A B55ALPHA; UNCLASSIFIED DRUG; VIRUS PROTEIN;

ADENOVIRUS; ALPHA HELIX; ARTICLE; BINDING SITE; CELL DEATH; CONTROLLED STUDY; IMMUNOPRECIPITATION; MUTATIONAL ANALYSIS; NONHUMAN; PREDICTION; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE;

ADENOVIRUS; BIOINFORMATICS; PP2A; PROTEIN-PROTEIN INTERACTIONS; SIGNAL TRANSDUCTION;

ADENOVIRUS E4 PROTEINS; AMINO ACID MOTIFS; AMINO ACID SUBSTITUTION; ANIMALS; APOPTOSIS; BINDING SITES; CONSERVED SEQUENCE; HEK293 CELLS; HUMANS; MOLECULAR DOCKING SIMULATION; PROTEIN BINDING; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN PHOSPHATASE 2; PROTEIN STRUCTURE, SECONDARY; RATS; STRUCTURAL HOMOLOGY, PROTEIN;

EID: 84877702809     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.343756     Document Type: Article

References (49)

1. Ben-Israel, H., Sharf, R., Rechavi, G., and Kleinberger, T. (2008) Adenovirus E4 or f4 protein down-regulates MYC expression through interaction with the PP2A-B55 subunit. J. Virol. 82, 9381-9388
2. Bondesson, M., Ohman, K., Manervik, M., Fan, S., and Akusjärvi, G. (1996) Adenovirus E4 open reading 4 protein autoregulates E4 transcription by inhibiting E1A transactivation of the E4 promoter. J. Virol. 70, 3844-3851
3. Mannervik, M., Fan, S., Ström, A. C., Helin, K., and Akusjärvi, G. (1999) Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein. Virology 256, 313-321
4. Medghalchi, S., Padmanabhan, R., and Ketner, G. (1997) Early region 4 modulates adenovirus DNA replication by two genetically separable mechanisms. Virology 236, 8-17
5. Müller, U., Kleinberger, T., and Shenk, T. (1992) Adenovirus E4 or f4 protein reduces phosphorylation of c-fos and E1A proteins while simultaneously reducing the level of AP-1. J. Virol. 66, 5867-5878
6. Estmer Nilsson, C., Petersen-Mahrt, S., Durot, C., Shtrichman, R., Krainer, A. R., Kleinberger, T., and Akusjärvi, G. (2001) The adenovirus E4-ORF4 splicing enhancer protein interacts with a subset of phosphorylated SR proteins. EMBO J. 20, 864-871
7. Kanopka, A., Mühlemann, O., Petersen-Mahrt, S., Estmer, C., Ohrmalm, C., and Akusjärvi, G. (1998) Regulation of adenovirus alternative RNA splicing by dephosphorylation of SR proteins. Nature 393, 185-187
8. O'Shea, C., Klupsch, K., Choi, S., Bagus, B., Soria, C., Shen, J., McCormick, F., and Stokoe, D. (2005) Adenoviral proteins mimic nutrient/growth signals to activate the mTOR pathway for viral replication. EMBO J. 24, 1211-1221
9. Ben-Israel, H., and Kleinberger, T. (2002) Adenovirus and cell cycle control. Front. Biosci. 7, d1369-d1395
10. Kornitzer, D., Sharf, R., and Kleinberger, T. (2001) Adenovirus E4 or f4 protein induces PP2A-dependent growth arrest in S. cerevisiae and interacts with the anaphase promoting complex/cyclosome. J. Cell Biol. 154, 331-344
11. Li, S., Szymborski, A., Miron, M. J., Marcellus, R., Binda, O., Lavoie, J. N., and Branton, P. E. (2009) The adenovirus E4 or f4 protein induces growth arrest and mitotic catastrophe in H1299 human lung carcinoma cells. Oncogene 28, 390-400
12. Shtrichman, R., Sharf, R., Barr, H., Dobner, T., and Kleinberger, T. (1999) Induction of apoptosis by adenovirus E4 or f4 protein is specific to transformed cells and requires an interaction with protein phosphatase 2A. Proc. Natl. Acad. Sci. U.S.A. 96, 10080-10085
13. Afifi, R., Sharf, R., Shtrichman, R., and Kleinberger, T. (2001) Selection of apoptosis-deficient adenovirus E4 or f4 mutants in Saccharomyces cerevisiae. J. Virol. 75, 4444-4447
14. Maoz, T., Koren, R., Ben-Ari, I., and Kleinberger, T. (2005)YND1interacts with CDC55 and is a novel mediator of E4 or f4-induced toxicity. J. Biol. Chem. 280, 41270-41277
15. Roopchand, D. E., Lee, J. M., Shahinian, S., Paquette, D., Bussey, H., and Branton, P. E. (2001) Toxicity of human adenovirus E4 or f4 protein in Saccharomyces cerevisiae results from interactions with the Cdc55 regulatory B subunit of PP2A. Oncogene 20, 5279-5290
16. Kleinberger, T., and Shenk, T. (1993) Adenovirus E4 or f4 protein binds to protein phosphatase 2A, and the complex down-regulates E1A-enhanced junB transcription. J. Virol. 67, 7556-7560
17. Shtrichman, R., Sharf, R., and Kleinberger, T. (2000) Adenovirus E4 or f4 protein interacts with both Bα and B′ subunits of protein phosphatase 2A, but E4 or f4-induced apoptosis is mediated only by the interaction with Bα. Oncogene 19, 3757-3765
18. Brestovitsky, A., Sharf, R., Mittelman, K., and Kleinberger, T. (2011) The adenovirus E4 or f4 protein targets PP2A to the ACF chromatin-remodeling factor and induces cell death through regulation of SNF2h-containing complexes. Nucleic Acids Res. 39, 6414-6427
19. Champagne, C., Landry, M. C., Gingras, M. C., and Lavoie, J. N. (2004) Activation of adenovirus type 2 early region 4 ORF4 cytoplasmic death function by direct binding to Src kinase domain. J. Biol. Chem. 279, 25905-25915
20. Lavoie, J. N., Champagne, C., Gingras, M.-C., and Robert, A. (2000) Adenovirus E4 open reading frame 4-induced apoptosis involves dysregulation of Src family kinases. J. Cell Biol. 150, 1037-1056
21. Marcellus, R. C., Chan, H., Paquette, D., Thirlwell, S., Boivin, D., and Branton, P. E. (2000) Induction of p53-independent apoptosis by the adenovirus E4 or f4 protein requires binding to the Bα subunit of protein phosphatase 2A. J. Virol. 74, 7869-7877
22. Eichhorn, P. J., Creyghton, M. P., and Bernards, R. (2009) Protein phosphatase 2A regulatory subunits and cancer. Biochim. Biophys. Acta 1795, 1-15
23. Kleinberger, T. (2004) Induction of transformed cell-specific apoptosis by the adenovirus E4 or f4 protein. Prog. Mol. Subcell. Biol. 36, 245-267
24. Li, S., Brignole, C., Marcellus, R., Thirlwell, S., Binda, O., McQuoid, M. J., Ashby, D., Chan, H., Zhang, Z., Miron, M. J., Pallas, D. C., and Branton, P. E. (2009) The adenovirus E4 or f4 protein induces G2/M Arrest and cell death by blocking PP2A activity regulated by the B55 subunit. J. Virol. 83, 8340-8352
25. Marcellus, R. C., Lavoie, J. N., Boivin, D., Shore, G. C., Ketner, G., and Branton, P. E. (1998) The early region 4 orf4 protein of human adenovirus type 5 induces p53-independent cell death by apoptosis. J. Virol. 72, 7144-7153
26. Koren, R., Rainis, L., and Kleinberger, T. (2004) The scaffolding A/Tpd3 subunit and high phosphatase activity are dispensable for Cdc55 function in the Saccharomyces cerevisiae spindle checkpoint and in cytokinesis. J. Biol. Chem. 279, 48598-48606
27. Zhang, Z., Mui, M. Z., Chan, F., Roopchand, D. E., Marcellus, R. C., Blanchette, P., Li, S., Berghuis, A. M., and Branton, P. E. (2011) Genetic analysis of B55′/Cdc55 protein phosphatase 2A subunits. Association with the adenovirus E4 or f4 protein. J. Virol. 85, 286-295
28. Xu, Y., Chen, Y., Zhang, P., Jeffrey, P. D., and Shi, Y. (2008) Structure of a protein phosphatase 2A holoenzyme. Insights into B55-mediated Tau dephosphorylation. Mol. Cell 31, 873-885
29. Shtrichman, R., and Kleinberger, T. (1998) Adenovirus type 5 E4 open reading frame 4 protein induces apoptosis in transformed cells. J. Virol. 72, 2975-2982
30. Brestovitsky, A., Sharf, R., and Kleinberger, T. (2012) Preparation of cell lines for conditional knockdown of gene expression and measurement of the knockdown effects on E4 or f4-induced cell death. J. Vis. Exp. 68, 4442
31. Altschul, S. F., Gish, W., Miller, W., Myers, E. W., and Lipman, D. J. (1990) Basic local alignment search tool. J. Mol. Biol. 215, 403-410
32. Ashkenazy, H., Erez, E., Martz, E., Pupko, T., and Ben-Tal, N. ConSurf 2010. Calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic Acids Res. 38, W529-W533
33. Berezin, C., Glaser, F., Rosenberg, J., Paz, I., Pupko, T., Fariselli, P., Casadio, R., and Ben-Tal, N. (2004) ConSeq. The identification of functionally and structurally important residues in protein sequences. Bioinformatics 20, 1322-1324
34. Glaser, F., Pupko, T., Paz, I., Bell, R. E., Bechor-Shental, D., Martz, E., and Ben-Tal, N. (2003) ConSurf. Identification of functional regions in proteins by surface-mapping of phylogenetic information. Bioinformatics 19, 163-164
35. Landau, M., Mayrose, I., Rosenberg, Y., Glaser, F., Martz, E., Pupko, T., and Ben-Tal, N. (2005) ConSurf 2005. The projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res. 33, W299-W302
36. Neuvirth, H., Raz, R., and Schreiber, G. (2004) ProMate. A structure based prediction program to identify the location of protein-protein binding sites. J. Mol. Biol. 338, 181-199
37. Xu, D., and Zhang, Y. (2012) Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field. Proteins 80, 1715-1735
38. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., and Ferrin, T. E. (2004) UCSF Chimera. Avisualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612
39. Sippl, M. J. (1993) Recognition of errors in three-dimensional structures of proteins. Proteins 17, 355-362
40. Wiederstein, M., and Sippl, M. J. (2007) ProSA-web. Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res. 35, W407-W410
41. Andrusier, N., Nussinov, R., and Wolfson, H. J. (2007) Fire Dock. Fast interaction refinement in molecular docking. Proteins 69, 139-159
42. Mashiach, E., Nussinov, R., and Wolfson, H. J. (2010) Fiber Dock. A web server for flexible induced-fit backbone refinement in molecular docking. Nucleic Acids Res. 38, W457-W461
43. Schneidman-Duhovny, D., Inbar, Y., Nussinov, R., and Wolfson, H. J. (2005) Patch Dock and Symm Dock. Servers for rigid and symmetric docking. Nucleic Acids Res. 33, W363-W367
44. Comeau, S. R., Gatchell, D. W., Vajda, S., and Camacho, C. J. (2004) Clus-Pro. A fully automated algorithm for protein-protein docking. Nucleic Acids Res. 32, W96-W99
45. Comeau, S. R., Gatchell, D. W., Vajda, S., and Camacho, C. J. (2004) Clus-Pro. An automated docking and discrimination method for the prediction of protein complexes. Bioinformatics 20, 45-50
46. Kozakov, D., Brenke, R., Comeau, S. R., and Vajda, S. (2006) PIPER. An FFT-based protein docking program with pairwise potentials. Proteins 65, 392-406
47. Lavoie, J. N., Nguyen, M., Marcellus, R. C., Branton, P. E., and Shore, G. C. (1998) E4 or f4, a novel adenovirus death factor that induces p53-independent apoptosis by a pathway that is not inhibited by zVAD-fmk. J. Cell Biol. 140, 637-645
48. Livne, A., Shtrichman, R., and Kleinberger, T. (2001) Caspase activation by adenovirus E4 or f4 protein is cell line-specific and is mediated by the death receptor pathway. J. Virol. 75, 789-798
49. Eichhorn, P. J., Creyghton, M. P., Wilhelmsen, K., van Dam, H., and Bernards, R. (2007) A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC. PLoS Genet. 3, e218