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  • Original Paper
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A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing

Abstract

We describe here the definition and characterization of antigen CT-8/HOM-TES-85 encoded by a previously unknown gene and identified by serological expression screening using antibodies from a seminoma patient. Intriguingly, the leucine zipper region of CT-8/HOM-TES-85 shows an atypical amphipathy with clusters of hydrophobic residues that is exclusively shared by the N-myc proto-oncogene. CT-8/HOM-TES-85 gene is tightly silenced in normal tissues except for testis. However, it is frequently activated in human neoplasms of different types including lung cancer, ovarian cancer, melanoma and glioma. Endogenous as well as heterogeneously expressed CT-8/HOM-TES-85 targets predominantly to the nucleus forming a distinctive speckled pattern of nuclear dots arranged in macromolecular structures. By co-localization studies these speckles were identified as loci of transcriptional activity and splicing, suggesting that CT-8/HOM-TES-85 may be involved in these processes. The aberrant expression of CT-8/HOM-TES-85 in human neoplasms might therefore be involved in cancer associated alterations of transcriptional or post-transcriptional processes and thus may disclose new mechanisms involved in the manifestation of the cancer phenotype.

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References

  • Andrade LE, Chan EK, Raska I, Peebles CL, Roos G, Tan EM . 1991 J. Exp. Med., 173: 1407–1419

  • Bergsagel PL, Victor-Kobrin C, Brents LA, Mushinski JF, Kuehl WM . 1992 Curr. Top. Microbiol. Immunol. 182: 223–228

  • Boel P, Wildmann C, Sensei ML, Brasseur R, Renauld M, Coulie P, Boon T, van der Bruggen P . 1995 Immunity 2: 167–175

  • Boon T, Old LJ . 1997 Curr. Opin. Immunol. 9: 681–683

  • Boon T, Coulie PG, Van den Eynde B . 1997 Immunol. Today 18: 267–268

  • Chan EK, Sullivan KF, Fox RI, Tan EM . 1989 J. Autoimmun. 2: 321–327

  • Chen YT, Scanlan MJ, Sahin U, Türeci Ö, Güre AO, Tsang S, Williamson B, Stockert E, Pfreundschuh M, Old LJ . 1997 Proc. Natl. Acad. Sci. USA 94: 1914–1918

  • Chen YT, Old LJ . 1999 Cancer J. Sci. Am. 5: 16–17

  • Deleage G, Roux B . 1987 Protein Eng. 1: 289–294

  • De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur F, Boon T . 1996 Proc. Natl. Acad. Sci. USA 93: 7149–7153

  • De Smet C, Lurquin C, Lethe B, Martelange V, Boon T . 1999 Mol. Cell. Biol. 19: 7327–7335

  • Diatchenko L, Lau YF, Campbell AP, Chenchik A, Moqadam F, Huang B, Lukyanov S, Lukyanov K, Gurskaya N, Sverdlov ED, Siebert PD . 1996 Proc. Natl. Acad. Sci. USA 93: 6025–6030

  • Disis ML, Cheever MA . 1996 Curr. Opin. Immunol. 8: 637–642

  • Eichmüller S, Usener D, Dummer R, Stein A, Thiel D, Schadendorf D . 2001 Proc. Natl. Acad. Sci. USA 98: 629–634

  • Fu XD, Maniatis T . 1990 Nature 343: 437–441

  • Garnier J, Gibrat JF, Robson B . 1996 Methods Enzymol. 266: 540–553

  • Gaugler B, Van den Eynde B, van der Bruggen P, Romero R, Gafario JJ, De Plaen E, Lethe B, Brasseur G, Boon T . 1995 J. Exp. Med. 79: 921–930

  • Gentz R, Rauscher FJ, Abate C, Curran T . 1989 Science 243: 1695–1699

  • Geourjon C, Deleage G . 1995 Comput. Appl. Biosci. 11: 681–684

  • Güre A, Stockert E, Scanlan MJ, Keresztes RS, Jager D, Altorki NK, Old LJ, Chen YT . 2000 Proc. Natl. Acad. Sci. USA 97: 4198–4203

  • Halle JP, Meisterernst M . 1996 Trends Genet. 12: 161–163

  • Kallenberg CG . 1990 Clin. Rheumatol. 9S1: 136–139

  • Kim J, Noskov VN, Lu X, Bergmann A, Ren X, Warth T, Richardson P, Kouprina N, Stubbs L . 2000 Genome Res. 10: 1138–1147

  • Kouzarides T, Ziff E . 1988 Nature 336: 646–651

  • Kramer H, Phistry M . 1996 J. Cell Biol. 133: 1205–1215

  • Lethe B, Lucas S, Michaux L, De Smet C, Godelaine D, Serrano A, De Plaen E, Boon T . 1998 Int. J. Cancer 76: 903–908

  • Lim FI, Soulez M, Koczan D, Thiesen HJ, Knight JC . 1998 Oncogene 17: 2013–2018

  • Mandruzzato S, Brasseur F, Andry G, Boon T, van der Bruggen P . 1997 J. Exp. Med. 186: 785–793

  • McCauliffe DP, Lux FA, Lieu TS, Sanz I, Hanke J, Newkirk MM, Siciliano MJ, Sontheimer RD, Capra JD . 1989 J. Autoimmun. 2: 375–381

  • Meuwissen RJL, Meerts JMN, Hoovers NJ, Leschot T, Heyting C . 1997 Genomics 37: 101–106

  • Nakai K, Horton P . 1999 Trends Biochem. Sci. 24: 34–36

  • Neugebauer KM, Roth MB . 1997 Genes Dev. 11: 1148–1159

  • Ochs RL, Lischwe MA, Spohn WH, Busch H . 1985 Biol. Cell 54: 123–133

  • Old LJ, Chen YT . 1998 J. Exp. Med. 187: 1163–1167

  • Ono T, Kurashige T, Harada N, Noguchi Y, Saika T, Niikawa N, Aoe M, Nakamura S, Higashi T, Hiraki A, Wada H, Kumon H, Old LJ, Nakayama E . 2001 Proc. Natl. Acad. Sci. USA 98: 3282–3287

  • Rubinfeld B, Albert I, Porfiri E, Munemitsu S, Polakis P . 1997 Cancer Res. 57: 462–463

  • Sahin U, Türeci Ö, Schmitt H, Cochlovius B, Johannes T, Schmits R, Pfreundschuh M . 1995 Proc. Natl. Acad. Sci. USA 92: 11810–11813

  • Sahin U, Türeci Ö, Pfreundschuh M . 1997 Curr. Opin. Immunol. 9: 709–716

  • Sahin U, Türeci Ö, Chen YT, Seitz G, Villena C, Old LJ, Pfreundschuh M . 1998 Int. J. Cancer 78: 387–389

  • Sleeman JE, Lamond AI . 1999 Curr. Opin. Cell. Biol. 11: 372–377

  • Stockert E, Jager E, Chen YT, Scanlan MJ, Gout I, Karbach J, Arand M, Knuth A, Old LJ . 1998 J. Exp. Med. 187: 1349–1354

  • Szostecki C, Krippner H, Penner E, Bautz FA . 1987 Clin. Exp. Immunol. 68: 108–116

  • Türeci Ö, Sahin U, Schobert I, Koslowski M, Schmitt H, Schild HJ, Stenner F, Seitz G, Rammensee HG, Pfreundschuh M . 1996 Cancer Res. 56: 4766–4772

  • Türeci Ö, Sahin U, Zwick C, Koslowski M, Seitz G, Pfreundschuh M . 1998 Proc. Natl. Acad. Sci. USA 95: 5211–5216

  • Türeci Ö, Sahin U, Pfreundschuh M . 1997 Mol. Med. Today 3: 342–349

  • Turner R, Tjian R . 1989 Science 243: 1689–1694

  • van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, van den Eynde B, Knuth A, Boon T . 1991 Science 254: 1643–1647

  • Venrooij WJ, Sillikens PT . 1989 Clin. Exp. Rheumatol. 7: 635–645

  • Wang J, Cao LG, Wang YL, Pederson T . 1991 Proc. Natl. Acad. Sci. USA 88: 7391–7395

  • Wang RF, Wang X, Atwood AC, Topalian SL, Rosenberg SA . 1999 Science 284: 1351–1354

  • Wei X, Somanathan S, Samarabandu J, Berezney R . 1999 J. Cell Biol. 146: 543–558

  • Wölfel T, Hauer M, Schneider J, Serrano M, Wölfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Buschenfelde KH, Beach D . 1995 Science 269: 1281–1284

  • Wynshaw-Boris A, Gambello MJ . 2001 Genes Dev. 15: 639–651

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Acknowledgements

We thank Mr Uli Luxemburger, Mrs Evi Regitz and Mr Michael Becker for excellent technical assistance. This work was supported in parts by the Sonderforschungsbereich 399 and 432, by Deutsche Forschungsgemeinschaft (TU 115/1-2 and SA 776/2-1), the BIOMED II program and the 5th FP of the European Commission.

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Correspondence to Ugur Sahin.

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Türeci, Ö., Sahin, U., Koslowski, M. et al. A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing. Oncogene 21, 3879–3888 (2002). https://doi.org/10.1038/sj.onc.1205481

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