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  • Original Paper
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PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation

Oncogene volume 24, pages 1982–1993 (2005)Cite this article

Abstract

The proto-oncoprotein c-Myc functions as a transcriptional regulator that controls different aspects of cell behavior, including proliferation, differentiation, and apoptosis. In addition, Myc proteins have the potential to transform cells and are deregulated in the majority of human cancers. Several Myc-interacting factors have been described that mediate part of Myc's functions in the control of cell behavior. Here, we describe the isolation of a novel 150 kDa protein, designated PARP-10, that interacts with Myc. PARP-10 possesses domains with homology to RNA recognition motifs and to poly(ADP-ribose) polymerases (PARP). Molecular modeling and biochemical analysis define a PARP domain that is capable of ADP-ribosylating PARP-10 itself and core histones, but neither Myc nor Max. PARP-10 is localized to the nuclear and cytoplasmic compartments that is controlled at least in part by a Leu-rich nuclear export sequence (NES). Functionally, PARP-10 inhibits c-Myc- and E1A-mediated cotransformation of rat embryo fibroblasts, a function that is independent of PARP activity but that depends on a functional NES. Together, our findings define a novel PARP enzyme involved in the control of cell proliferation.

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References

  • Ame JC, Rolli V, Schreiber V, Niedergang C, Apiou F, Decker P, Muller S, Hoger T, Menissier-de Murcia J and de Murcia G . (1999). J. Biol. Chem., 274, 17860–17868.

  • Ame JC, Spenlehauer C and de Murcia G . (2004). BioEssays, 26, 882–893.

  • Augustin A, Spenlehauer C, Dumond H, Menissier-De Murcia J, Piel M, Schmit AC, Apiou F, Vonesch JL, Kock M, Bornens M and De Murcia G . (2003). J. Cell. Sci., 116, 1551–1562.

  • Bouchard C, Dittrich O, Kiermaier A, Dohmann K, Menkel A, Eilers M and Luscher B . (2001). Genes Dev., 15, 2042–2047.

  • Bouchard VJ, Rouleau M and Poirier GG . (2003). Exp. Hematol., 31, 446–454.

  • Boxer LM and Dang CV . (2001). Oncogene, 20, 5595–5610.

  • Burkle A . (2001). BioEssays, 23, 795–806.

  • Carson M . (1991). J. Appl. Crystallogr., 24, 946–950.

  • Cerni C, Bousset K, Seelos C, Burkhardt H, Henriksson M and Luscher B . (1995). Oncogene, 11, 587–596.

  • Cheng SW, Davies KP, Yung E, Beltran RJ, Yu J and Kalpana GV . (1999). Nat. Genet., 22, 102–105.

  • Chi NW and Lodish HF . (2000). J. Biol. Chem., 275, 38437–38444.

  • Conte MR, Grune T, Ghuman J, Kelly G, Ladas A, Matthews S and Curry S . (2000). EMBO J., 19, 3132–3141.

  • Cook BD, Dynek JN, Chang W, Shostak G and Smith S . (2002). Mol. Cell. Biol., 22, 332–342.

  • Crowder SM, Kanaar R, Rio DC and Alber T . (1999). Proc. Natl. Acad. Sci. USA, 96, 4892–4897.

  • Dallaire F, Dupuis S, Fiset S and Chabot B . (2000). J. Biol. Chem., 275, 14509–14516.

  • D'Amours D, Desnoyers S, D'Silva I and Poirier GG . (1999). Biochem. J., 342 (Part 2), 249–268.

  • de Murcia JM, Niedergang C, Trucco C, Ricoul M, Dutrillaux B, Mark M, Oliver FJ, Masson M, Dierich A, LeMeur M, Walztinger C, Chambon P and de Murcia G . (1997). Proc. Natl. Acad. Sci. USA, 94, 7303–7307.

  • Domingues FS, Koppensteiner WA, Jaritz M, Prlic A, Weichenberger C, Wiederstein M, Floeckner H, Lackner P and Sippl MJ . (1999). Proteins, 3, 112–120.

  • Dreyfuss G, Hentze M and Lamond AI . (1996). Cell, 85, 963–972.

  • Fiset S and Chabot B . (2001). Nucleic. Acids Res., 29, 2268–2275.

  • Fornerod M, Ohno M, Yoshida M and Mattaj IW . (1997). Cell, 90, 1051–1060.

  • Frank SR, Parisi T, Taubert S, Fernandez P, Fuchs M, Chan HM, Livingston DM and Amati B . (2003). EMBO Rep., 4, 575–580.

  • Frank SR, Schroeder M, Fernandez P, Taubert S and Amati B . (2001). Genes Dev., 15, 2069–2082.

  • Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M and Nishida E . (1997). Nature, 390, 308–311.

  • Ginisty H, Amalric F and Bouvet P . (2001). J. Biol. Chem., 276, 14338–14343.

  • Grandori C, Cowley SM, James LP and Eisenman RN . (2000). Annu. Rev. Cell Dev. Biol., 16, 653–699.

  • Hassa PO and Hottiger MO . (2002). Cell. Mol. Life Sci., 59, 1534–1553.

  • Henriksson M and Luscher B . (1996). Adv. Cancer Res., 68, 109–182.

  • Jenuwein T and Allis CD . (2001). Science, 293, 1074–1080.

  • Kawamitsu H, Hoshino H, Okada H, Miwa M, Momoi H and Sugimura T . (1984). Biochemistry, 23, 3771–3777.

  • Kickhoefer VA, Siva AC, Kedersha NL, Inman EM, Ruland C, Streuli M and Rome LH . (1999). J. Cell Biol., 146, 917–928.

  • Kim H, Jacobson MK, Rolli V, Menissier-de Murcia J, Reinbolt J, Simonin F, Ruf A, Schulz G and de Murcia G . (1997). Biochem. J., 322 (Part 2), 469–475.

  • Kraus WL and Lis JT . (2003). Cell, 113, 677–683.

  • Lichter P, Tang CJ, Call K, Hermanson G, Evans GA, Housman D and Ward DC . (1990). Science, 247, 64–69.

  • Liu X, Tesfai J, Evrard YA, Dent SY and Martinez E . (2003). J. Biol. Chem., 278, 20405–20412.

  • Luscher B . (2001). Gene, 277, 1–14.

  • Luscher-Firzlaff JM, Westendorf JM, Zwicker J, Burkhardt H, Henriksson M, Muller R, Pirollet F and Luscher B . (1999). Oncogene, 18, 5620–5630.

  • Lyons RJ, Deane R, Lynch DK, Ye ZS, Sanderson GM, Eyre HJ, Sutherland GR and Daly RJ . (2001). J. Biol. Chem., 276, 17172–17180.

  • Macara IG . (2001). Microbiol. Mol. Biol. Rev., 65, 570–594, table of contents.

  • Masutani M, Nozaki T, Nakamoto K, Nakagama H, Suzuki H, Kusuoka O, Tsutsumi M and Sugimura T . (2000). Mutat. Res., 462, 159–166.

  • Mattaj IW and Englmeier L . (1998). Annu. Rev. Biochem., 67, 265–306.

  • Matthias P, Muller MM, Schreiber E, Rusconi S and Schaffner W . (1989). Nucleic Acids Res., 17, 6418.

  • McMahon SB, Wood MA and Cole MD . (2000). Mol. Cell. Biol., 20, 556–562.

  • Menissier de Murcia J, Ricoul M, Tartier L, Niedergang C, Huber A, Dantzer F, Schreiber V, Ame JC, Dierich A, LeMeur M, Sabatier L, Chambon P and de Murcia G . (2003). EMBO J., 22, 2255–2263.

  • Michael WM . (2000). Trends Cell. Biol., 10, 46–50.

  • Nakielny S and Dreyfuss G . (1999). Cell, 99, 677–690.

  • Nesbit CE, Tersak JM and Prochownik EV . (1999). Oncogene, 18, 3004–3016.

  • Nikiforov MA, Chandriani S, Park J, Kotenko I, Matheos D, Johnsson A, McMahon SB and Cole MD . (2002). Mol. Cell. Biol., 22, 5054–5063.

  • Oei SL and Shi Y . (2001). Biochem. Biophys. Res. Commun., 285, 27–31.

  • Oster SK, Ho CS, Soucie EL and Penn LZ . (2002). Adv. Cancer Res., 84, 81–154.

  • Park J, Kunjibettu S, McMahon SB and Cole MD . (2001). Genes Dev., 15, 1619–1624.

  • Park J, Wood MA and Cole MD . (2002). Mol. Cell. Biol., 22, 1307–1316.

  • Polo S, Confalonieri S, Salcini AE and Di Fiore PP . (2003). Sci. STKE, 2003, re17.

  • Poortinga G, Hannan KM, Snelling H, Walkley CR, Jenkins A, Sharkey K, Wall M, Brandenburger Y, Palatsides M, Pearson RB, McArthur GA and Hannan RD . (2004). EMBO J., 23, 3325–3335.

  • Ruf A, Mennissier de Murcia J, de Murcia G and Schulz GE . (1996). Proc. Natl. Acad. Sci. USA, 93, 7481–7485.

  • Sbodio JI, Lodish HF and Chi NW . (2002). Biochem. J., 361, 451–459.

  • Schreiber V, Ame JC, Dolle P, Schultz I, Rinaldi B, Fraulob V, Menissier-de Murcia J and de Murcia G . (2002). J. Biol. Chem., 277, 23028–23036.

  • Simonin F, Menissier-de Murcia J, Poch O, Muller S, Gradwohl G, Molinete M, Penning C, Keith G and de Murcia G . (1990). J. Biol. Chem., 265, 19249–19256.

  • Sippl MJ . (1993). Proteins, 17, 355–362.

  • Smith S . (2001). Trends Biochem. Sci., 26, 174–179.

  • Smith S and de Lange T . (2000). Curr. Biol., 10, 1299–1302.

  • Smith S, Giriat I, Schmitt A and de Lange T . (1998). Science, 282, 1484–1487.

  • Sommer A, Bousset K, Kremmer E, Austen M and Luscher B . (1998). J. Biol. Chem., 273, 6632–6642.

  • Sommer A, Hilfenhaus S, Menkel A, Kremmer E, Seiser C, Loidl P and Luscher B . (1997). Curr. Biol., 7, 357–365.

  • Sterner DE and Berger SL . (2000). Microbiol. Mol. Biol. Rev., 64, 435–459.

  • Strahl BD and Allis CD . (2000). Nature, 403, 41–45.

  • Tong WM, Cortes U and Wang ZQ . (2001). Biochim. Biophys. Acta, 1552, 27–37.

  • Tulin A and Spradling A . (2003). Science, 299, 560–562.

  • Tulin A, Stewart D and Spradling AC . (2002). Genes Dev., 16, 2108–2119.

  • van Gunsteren WF, Billeter SR, Eising AA, Hünenberger PH, Krüger P, Mark AE, Scott WRP and Tironi IG . (1996). Biomolecular Simulation: The GROMOS96 Manual and User Guide. vdf Hochschulverlag AG: Zürich.

    Google Scholar 

  • Vervoorts J, Luscher-Firzlaff JM, Rottmann S, Lilischkis R, Walsemann G, Dohmann K, Austen M and Luscher B . (2003). EMBO Rep., 4, 484–490.

  • Vriend G . (1990). J. Mol. Graph., 8, 52–56.

  • Wang ZQ, Stingl L, Morrison C, Jantsch M, Los M, Schulze-Osthoff K and Wagner EF . (1997). Genes Dev., 11, 2347–2358.

  • Xu D, Popov N, Hou M, Wang Q, Bjorkholm M, Gruber A, Menkel AR and Henriksson M . (2001). Proc. Natl. Acad. Sci. USA, 98, 3826–3831.

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Acknowledgements

We thank H Ariga, P Bouvet, R Eisenman, H Eilers, S Oei and M Yoshida, for reagents and H Burkhardt, A Graf, M Hajek, G Schmidt and J Stahl for expert technical assistance. This work was supported by EMBO, DAAD, and Alexander von Humboldt fellowships to KL and EP, Jubiläumsfond der Österreichischen National bank to CS and by the START program of the Medical School of the RWTH to JL-F.

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Author notes

  1. Krzysztof Lesniewicz & Elzbieta Poreba

    Present address: Institute of Molecular Biology and Biotechnology, AM University, Miedzychodzka 5, 60-371, Poznan, Poland

  2. Matthias Austen

    Present address: Develogen AG, Rudolf-Wissell-Strasse 28, 37079, Göttingen, Germany

  3. Christa Cerni: Deceased on December 26, 2003.

Authors and Affiliations

  1. Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Klinikum der RWTH, Pauwelsstrasse 30, 52057, Aachen, Germany

    Mei Yu, Krzysztof Lesniewicz, Elzbieta Poreba, Gesa Walsemann, Juliane Lüscher-Firzlaff & Bernhard Lüscher

  2. Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

    Sabine Schreek, Jörg Vervoorts, Jürgen Mertsching & Matthias Austen

  3. Institut für Krebsforschung, Universität Wien, Borschkegasse 8a, 1090, Wien, Austria

    Christa Cerni & Chantal Schamberger

  4. Biochemisches Institut, Christian-Albrechts-Universität zu Kiel, Olshausenstr. 40, 24098, Kiel, Germany

    Joachim Grötzinger

  5. GSF-Institut für Molekulare Immunologie, Machioninistrasse 25, 81377, München, Germany

    Elisabeth Kremmer

  6. Institut für Humangenetik, Universität des Saarlandes, Kirrbergerstrasse, 66421, Homburg/Saar, Germany

    Yasmin Mehraein

  7. Max-Delbrück-Centrum, Proteinchemie, 13092, Berlin, Germany

    Regine Kraft

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Correspondence to Bernhard Lüscher.

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Yu, M., Schreek, S., Cerni, C. et al. PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. Oncogene 24, 1982–1993 (2005). https://doi.org/10.1038/sj.onc.1208410

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