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Adenovirus E1A requires the yeast SAGA histone acetyltransferase complex and associates with SAGA components Gcn5 and Tra1

Oncogene volume 21, pages 1411–1422 (2002)Cite this article

Abstract

The budding yeast Saccharomyces cerevisiae was used as a model system to study the function of the adenovirus E1A oncoprotein. Previously we demonstrated that expression of the N-terminal 82 amino acids of E1A in yeast causes pronounced growth inhibition and specifically interferes with SWI/SNF-dependent transcriptional activation. Further genetic analysis identified the yeast transcription factor Adr1 as a high copy suppressor of E1A function. Transcriptional activation by Adr1 requires interaction with co-activator proteins Ada2 and Gcn5, components of histone acetyltransferase complexes including ADA and SAGA. Analysis of mutant alleles revealed that several components of the SAGA complex, including proteins from the Ada, Spt, and Taf classes were required for E1A-induced growth inhibition. Growth inhibition also depended on the Gcn5 histone acetyltransferase, and point mutations within the Gcn5 HAT domain rendered cells E1A-resistant. Also required was SAGA component Tra1, a homologue of the mammalian TRRAP protein which is required for c-myc and E1A induced cellular transformation. Additionally, Gcn5 protein could associate with E1A in vitro in a manner that depended on the N-terminal domain of E1A, and Tra1 protein was co-immunoprecipitated with E1A in vivo. These results indicate a strong requirement for intact SAGA complex for E1A to function in yeast, and suggest a role for SAGA-like complexes in mammalian cell transformation.

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References

  • Aitsiali S, Ramirez S, Barre FX, Dkhissi F, Magnaghijaulin L, Girault JA, Robin P, Knibiehler M, Pritchard LL, Ducommun B, Trouche D, Harelbellan A . 1998 Nature 396: 184–186

  • Arndt KM, Ricupero-Hovasse S, Winston F . 1995 EMBO J. 14: 1490

  • Bayley ST, Mymryk JS . 1994 Int. J. Oncol. 5: 425–444

  • Benkirane M, Chun RF, Xiao H, Ogryzko VV, Howard BH, Nakatini Y, Jeang KT . 1998 J. Biol. Chem. 273: 24898–24905

  • Berger SL . 1999 Curr. Opin. Cell Biol. 11: 336–341

  • Berger SL, Cress WD, Cress A, Triezenberg SJ, Guarente L . 1990 Cell 61: 1199–1208

  • Berger SL, Pina B, Silverman N, Marcus GA, Agapite J, Regier JL, Triezenberg SJ, Guarente L . 1992 Cell 70: 251–265

  • Berk AJ, Boyer TG, Kapanidis AN, Ebright RH, Kobayashi NN, Horn PJ, Sullivan SM, Koop R, Surby MA, Triezenberg SJ . 1998 Cold Spring Harb. Symp. Quant. Biol. 63: 243–252

  • Bex F, Yin MJ, Burny A, Gaynor RB . 1998 Mol. Cell. Biol. 18: 2392–2405

  • Blanco JC, Minucci S, Lu J, Yang XJ, Walker KK, Chen H, Evans RM, Nakatini Y, Ozato K . 1998 Genes Dev. 12: 1638–1651

  • Burnham MR, Bruce-Staskal PJ, Harte MT, Weidow CL, Ma A, Weed SA, Bouton AH . 2000 Mol. Cell. Biol. 20: 5865–5878

  • Cairns BR . 1998 Trends in Biochem. Sci. 23: 20–25

  • Candau R, Berger SL . 1996 J. Biol. Chem. 271: 5237–5245

  • Candau R, Zhou JX, Allis CD, Berger SL . 1997 EMBO J. 16: 555–565

  • Chakravarti D, Ogryzko V, Kao HY, Nash A, Chen HW, Nakatani Y, Evans RM . 1999 Cell 96: 393–403

  • Chiang YC, Komarnitsky P, Chase D, Denis CL . 1996 J. Biol. Chem. 271: 32359–32365

  • Clark-Adams CD, Norris D, Osley MA, Fassler JS, Winston F . 1988 Genes Dev. 2: 150–159

  • Cosma MP, Tanaka T, Nasmyth K . 1999 Cell 97: 299–311

  • Dyson N, Harlow E . 1992 Cancer Surveys 12: 161–195

  • Eberharter A, Sterner DE, Schieltz D, Hassan A, Yates III JR, Berger SL, Workman JL . 1999 Mol. Cell. Biol. 19: 6621–6631

  • Eckner R, Ludlow JW, Lill NL, Oldread E, Arany Z, Modjtahedi N, DeCaprio JA, Livingston DM, Morgan JA . 1996 Mol. Cell. Biol. 16: 3454–3464

  • Eisenmann DM, Chapon C, Roberts SM, Dollard C, Winston F . 1994 Genetics 137: 647–657

  • Fassler JS, Winston F . 1988 Genetics 118: 203–212

  • Flint J, Shenk T . 1989 Annu. Rev. Genet. 23: 141–161

  • Gietz D, St Jean A, Woods RA, Schiestl RH . 1992 Nucleic Acids Res. 20: 1425

  • Grant PA, Duggan L, Cote J, Roberts SM, Brownell JE, Candau R, Ohba R, Owen-Hughes T, Allis CD, Winston F, Berger SL, Workman JL . 1997 Genes Dev. 11: 1640–1650

  • Grant PA, Schieltz D, Pray-Grant MG, Steger DJ, Reese JC, Yates III JR, Workman JL . 1998a Cell 94: 45–53

  • Grant PA, Schieltz D, Pray-Grant MG, Yates III JR, Workman JL . 1998b Molecular Cell 2: 863–867

  • Guldener U, Heck S, Fielder T, Beinhauer J, Hegemann JH . 1996 Nucleic Acids Res. 24: 2519–2524

  • Hahn S . 1998 Cell 95: 579–582

  • Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y, Kedes L . 1999 Cell 96: 405–413

  • Handa H, Toda T, Tajima M, Wada T, Iida H, Fukasawa T . 1987 Gene 58: 127–136

  • Hassan AH, Neely KE, Workman JL . 2001 Cell 104: 817–827

  • Hirschhorn JN, Brown SA, Clark CD, Winston F . 1992 Genes Dev. 6: 2288–2298

  • Jayachandra S, Low KG, Thlick AE, Yu J, Ling PD, Chang Y, Moore PS . 1999 Proc. Natl. Acad. Sci. USA 96: 11566–11571

  • Kiernan RE, Vanhulle C, Schiltz L, Adam E, Xiao H, Maudoux F, Calomme C, Burny A, Nakatani Y, Jeang KT, Benkirane M, Van Lint C . 1999 EMBO J. 18: 6106–6118

  • Komarnitsky PB, Klebanow ER, Weil PA, Denis CL . 1998 Mol. Cell. Biol. 18: 5861–5867

  • Kornberg RD, Lorch Y . 1999 Curr. Opin. Genet. Dev. 9: 148–151

  • Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK, Rosenfeld MG . 1998 Science 279: 703–707

  • Kraus VB, Inostroza JA, Yeung K, Reinberg D, Nevins JR . 1994 Proc. Natl. Acad. Sci. USA 91: 6279–6282

  • Krebs JE, Fry CJ, Samuels ML, Peterson CL . 2000 Cell 102: 587–598

  • Krumm A, Madisen L, Yang XJ, Goodman R, Nakatani Y, Groudine M . 1998 Proc. Natl. Acad. Sci. USA 95: 13501–13506

  • Kuo MH, Brownell JE, Sobel RE, Ranalli TA, Cook RG, Edmondson DG, Roth SY, Allis CD . 1996 Nature 383: 269–272

  • Kuo MH, Zhou J, Jambeck P, Churchill ME, Allis CD . 1998 Genes Dev. 12: 627–639

  • Lawrence CW . 1991 Meth. Enzymol. 194: 273–281

  • Logie C, Tse C, Hansen JC, Peterson CL . 1999 Biochemistry 38: 2514–2522

  • Marzio G, Tyagi M, Gutierrez MI, Giacca M . 1998 Proc. Natl. Acad. Sci. USA 95: 13519–13524

  • McMahon C, Suthiphongchai T, DiRenzo J, Ewen ME . 1999 Proc. Natl. Acad. Sci. USA 96: 5382–5387

  • McMahon SB, Van Buskirk HA, Dugan KA, Copeland TD, Cole MD . 1998 Cell 94: 363–374

  • Miller ME, Cairns BR, Levinson RS, Yamamoto KR, Engel DA, Smith MM . 1996 Mol. Cell. Biol. 16: 5737–5743

  • Miller ME, Engel DA, Smith MM . 1995 Oncogene 11: 1623–1630

  • Ogryzko VV, Kotani T, Zhang X, Schlitz RL, Howard T, Yang XJ, Howard BH, Qin J, Nakatani Y . 1998 Cell 94: 35–44

  • Patel D, Huang SM, Baglia LA, McCance DJ . 1999 EMBO J. 18: 5061–5072

  • Peterson CL . 1998 Cold Spring Harb. Symp. Quant. Biol. 63: 545–552

  • Peterson CL, Herskowitz I . 1992 Cell 68: 573–583

  • Pollard KJ, Peterson CL . 1997 Mol. Cell. Biol. 17: 6212–6222

  • Puri PL, Sartorelli V, Yang XJ, Hamamori Y, Ogryzko VV, Howard BH, Kedes L, Wang JY, Graessmann A, Nakatani Y, Levrero M . 1997 Molecular Cell 1: 35–45

  • Reid JL, Bannister AJ, Zegerman P, Martinez-Balbas MA, Kouzarides T . 1998 EMBO J. 17: 4469–4477

  • Roberts SM, Winston F . 1997 Genetics 147: 451–465

  • Robzyk K, Kassir Y . 1992 Nucleic Acids Research 20: 3790–

  • Ruley HE . 1983 Nature 304: 602–606

  • Saleh A, Schieltz D, Ting N, McMahon SB, Litchfield DW, Yates III JR, Lees-Miller SP, Cole MD, Brandl CJ . 1998 J. Biol. Chem. 273: 26559–26565

  • Sambrook J, Fritsch E, Maniatis T . 1989 Molecular Cloning: A Laboratory Manual Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

  • Sang N, Severino A, Russo P, Baldi A, Giordano A, Mileo AM, Paggi MG, De Luca A . 2001 J. Biol. Chem. 276: 27026–27033

  • Santisteban MS, Arents G, Moudrianakis EN, Smith MM . 1997 EMBO J. 16: 2493–2506

  • Sherman F, Fink G, Hicks J . 1982 Methods in Yeast Genetics Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

    Google Scholar 

  • Simchen G, Winston F, Styles CA, Fink GR . 1984 Proc. Natl. Acad. Sci. USA 81: 2431–2434

  • Sterner DE, Grant PA, Roberts SM, Duggan LJ, Belotserkovskaya R, Pacella LA, Winston F, Workman JL, Berger SL . 1999 Mol. Cell. Biol. 19: 86–98

  • Syntichaki P, Topalidou I, Thireos G . 2000 Nature 404: 414–417

  • Van den Elsen P, Houweling A, Van der Eb A . 1983 Virology 128: 377–390

  • Vassilev A, Yamauchi J, Kotani T, Prives C, Avantaggiati ML, Qin J, Nakatani Y . 1998 Molecular Cell 2: 869–875

  • Walker SS, Reese JC, Apone LM, Green MR . 1996 Nature 383: 185–188

  • Wang L, Grossman SR, Kieff E . 2000 Proc. Natl. Acad. Sci. USA 97: 430–435

  • Winston F, Chaleff DT, Valent B, Fink GR . 1984 Genetics 107: 179–197

  • Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y . 1996 Nature 382: 319–324

  • Zimmermann H, Degenkolbe R, Bernard HU, O'Connor MJ . 1999 J. Virol. 73: 6209–6219

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Acknowledgements

We thank David Allis and Shelley Berger for strains and plasmids and Patrick Grant for critically reading this manuscript. We also thank Ted Young for strains, plasmids and helpful discussions. CA Kulesza was supported in part by an NIH institutional training grant (5T32GM08136). This work was supported by grants from the National Institutes of Health awarded to DA Engel (CA60675 and CA87620) and MM Smith (GM28920).

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Authors and Affiliations

  1. Department of Microbiology and Cancer Center, University of Virginia School of Medicine, Charlottesville, 22908, Virginia, VA, USA

    Caroline A Kulesza, M Mitchell Smith & Daniel A Engel

  2. Department of Molecular Biology, Princeton University, New Jersey, 08544, NJ, USA

    Heather A Van Buskirk & Michael D Cole

  3. Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, 16802, PA, USA

    Joseph C Reese

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  1. Caroline A Kulesza
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  2. Heather A Van Buskirk
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Correspondence to Daniel A Engel.

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Kulesza, C., Van Buskirk, H., Cole, M. et al. Adenovirus E1A requires the yeast SAGA histone acetyltransferase complex and associates with SAGA components Gcn5 and Tra1. Oncogene 21, 1411–1422 (2002). https://doi.org/10.1038/sj.onc.1205201

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