Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor

Oncogene volume 18, pages 3954–3962 (1999)Cite this article

Abstract

Ewing's sarcoma (EWS) cells accumulate elevated steady-state levels of poly (ADP-ribose) polymerase (PARP) mRNA and protein. To understand the molecular mechanisms underlying PARP upregulation, we cloned and analysed the 5′-flanking region of the PARP gene from EWS cells. Nucleotide sequence analysis demonstrated no variations in the PARP promoter region in EWS cells. The PARP promoter encompasses multiple binding motifs for the ETS transcription factor. We have also observed that there is a coordinated up-regulation of the expression of both PARP and ETS1, relative to cells of other human tumor types expressing lower levels of PARP. Transient co-expression of ETS1 in EWS cells resulted in a strong enhancement of PARP-promoter activity. The participation of ETS in the regulation of PARP gene expression was further demonstrated in EWS cells stably transfected with Ets1 antisense cDNA constructs. Antisense-mediated down-regulation of endogenous ETS1 resulted in the inhibition of PARP expression in EWS cells, and sensitized these cells to ionizing radiation. These data provide support for ETS regulation of PARP expression levels, and implicate ETS transcription factors in the radiation response of EWS cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Ackerman SL, Minden AG and Yeung C-Y. . 1993 Proc. Natl. Acad. Sci. USA 90: 11865–11869.

  • Albor A, Flessate DM, Soussi T and Notario V. . 1994 Cancer Res. 54: 4502–4507.

  • Avila MA, Velasco JA, Smulson ME, Dritschilo A, Castro R and Notario V. . 1994 Yeast 10: 1003–1017.

  • Bassuk AG and Leiden JM. . 1997 Adv. Immunol. 64: 65–104.

  • Bhatia K, Pommier Y, Fornace A, Breitman T, Cherny B, Giri C and Smulson ME. . (1989). In: ADP-Ribose Transfer Reactions: Mechanisms and Biological Significance. Jacobson MK and Jacobson EL (eds).. Springer-Verlag: New York pp. 494–501.

    Book  Google Scholar 

  • Bhatia K, Kang VH, Stein GS, Bustin M, Cherney BW, Notario V, Hague SJ, Huppi K and Smulson ME. . 1990 J. Cell. Physiol. 144: 345–353.

  • Bories JC, Willerford DM, Grevin D, Davidson L, Camus A, Martin P, Stehelin D and Alt FW. . 1995 Nature 377: 635–638.

  • Boulukos KE, Pognonec P, Rabault B, Bergue A and Ghysdael J. . 1989 Mol. Cell. Biol. 9: 5718–5721.

  • Cepko CL, Roberts BE and Mulligan RC. . 1984 Cell 37: 1053–1062.

  • Cesarone CF, Scarabelli L, Scivassi AI, Izzo R, Menegazzi M, Carcereri D, Prati A, Orunesu M and Bertazzoni U. . 1990 Biochim. Biophys. Acta 1087: 241–246.

  • Cherny BW, McBride OW, Chen D, Alkhatib H, Bhatia KG, Hensley P and Smulson ME. . 1987 Proc. Natl. Acad. Sci. USA 84: 8370–8374.

  • Cleaver JE and Morgan WF. . 1991 Mutat. Res. 257: 1–18.

  • Delattre O, Zucman J, Plougastel CD, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, Aurias A and Thomas G. . 1992 Nature 359: 162–165.

  • De Murcia G, Menissier-de Murcia J and Schreiber V. . 1991 BioEssays 13: 455–462.

  • Ding R, Pommier Y, Kang VH and Smulson M. . 1992 J. Biol. Chem. 267: 12804–12812.

  • Hodge DR, Thompson DM, Panayiotakis A and Seth A. . 1995 Meth. Mol. Biol. 37: 409–421.

  • Huang CC, Papas TS and Bhat NK. . 1997 Oncogene 15: 851–856.

  • Ingolia DE, Al-Ubaidi MR, Yeung CY, Bigo HA, Wright DA and Kellems RE. . 1986 Mol. Cell. Biol. 6: 4458–4466.

  • Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT and Shapiro DN. . 1995 Oncogene 10: 1229–1234.

  • Jolliff K, Li Y and Johnson LF. . 1991 Nucl. Acids Res. 19: 2267–2274.

  • Jorgensen TJ, Notario V, Thraves PJ and Dritschilo A. . 1993 Radiat. Oncol. Invest. 1: 189–197.

  • Kovar H, Aryee DNT, Jug G, Henockl C, Schemper M, Delattre O, Thomas G and Gadner H. . 1996 Cell Growth Diff. 7: 429–437.

  • Küpper JH, Muller M, Jacobson MK, Tatsumi-Miyajima J, Coyle DL, Jacobson EL and Burkle A. . 1995 Mol. Cell. Biol. 15: 3154–3163.

  • Mavrothalassitis GJ, Watson DK and Papas TS. . 1990 Proc. Natl Acad. Sci. USA 87: 1047–1051.

  • May WA, Lessnick SL, Braun BS, Klemsz M, Lewis BC, Lunsford LB, Hromas R and Denny CT. . 1993 Proc. Natl Acad. Sci. USA 90: 5752–5756.

  • Moreau-Gachelin F. . 1994 Biochim. Biophys. Acta 1198: 149–163.

  • Negroni M and Bertazzoni U. . 1993 Biochim. Biophys. Acta 1173: 133–140.

  • Oei SL, Herzog H, Hirsch-Kauffmann M, Schneider R, Auer B and Schweiger M. . 1994 Mol. Cell. Biochem. 138: 99–104.

  • Oei SL, Griesenbeck J, Schweiger M, Babich V, Kropotov A and Tomilin N. . 1997 Biochem. Biophys. Res. Commun. 240: 108–111.

  • Ogura T, Nyunoya H, Takahashi-Masutani M, Miwa M, Sugimura T and Easumi H. . 1990 Biochem. Biophys. Res. Commun. 167: 701–710.

  • Ohno T, Rao VN and Reddy SP. . 1993 Cancer Res. 53: 5859–5863.

  • Papas TS, Bhat NK, Spyropoulos DD, Mjaatvedt AE, Vournakis J, Seth A and Watson DK. . 1997 Leukemia 11: 557–566.

  • Pearson BE, Nasheuer H-P and Wang TSF. . 1991 Mol. Cell. Biol. 11: 2081–2095.

  • Peter M, Couturier J, Pacquement H, Michon J, Thomas G, Magdelenat H and Delattre O. . 1997 Oncogene 14: 1159–1164.

  • Petersen JM, Skalicky JJ, Donaldson LW, McIntosh LP, Alber T and Graves BJ. . 1995 Science 269: 1866–1869.

  • Prasad SC, Thraves PJ, Bhatia KG, Smulson ME and Dritschilo A. . 1990 Cancer Res. 50: 38–43.

  • Robertson M. . 1988 Nature 336: 522–524.

  • Romano-Spica V, Georgiou P, Suzuki H, Papas TS and Bhat NK. . 1995 J. Immunol. 154: 2724–2732.

  • Satoh MS and Lindahl T. . 1992 Nature 356: 356–358.

  • Seth A and Papas TS. . 1990 Oncogene 5: 1761–1767.

  • Schreiber V, Hunting D, Trucco C, Gowans B, Grunwald D, DeMurcia G and DeMurcia JM. . 1995 Proc. Natl. Acad. Sci. USA 92: 4753–4757.

  • Schwachtgen JL, Janel N, Barek L, Duterque-Coquillaud M, Ghysdael J, Meyer D and Kerbiriou-Nabias D. . 1998 Oncogene 15: 3091–3102.

  • Soldatenkov VA, Prasad S, Notario V and Dritschilo A. . 1995 Cancer Res. 55: 4240–4242.

  • Soldatenkov VA, Dritschilo A, Wang F-H, Olah Z, Anderson WB and Kasid U. . 1997 Cancer J. Sci. Am. 3: 13–20.

  • Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ and Denny CT. . 1994 Nature Genet. 6: 146–151.

  • Thraves PJ, Bhatia K, Smulson ME and Dritschilo A. . 1989 In: ADP-Ribose Transfer Reactions: Mechanisms and Biological Significance. Jacobson MK and Jacobson EL (eds).. Springer-Verlag: New York pp. 520–524.

    Book  Google Scholar 

  • Velasco JA, Ramsamooj P, Thraves PJ, Eva A, Dritschilo A and Notario V. . 1995 Oncogene 10: 2253–2258.

  • Wang ZO, Auer B, Stingl L, Berghammer H, Haidacher D, Schweiger M and Wagner F. . 1995 Genes Dev. 9: 509–520.

  • Wasylyk B, Hahn SL and Giovane A. . 1993 Eur. J. Biochem. 211: 7–18.

  • Wein KH, Netzker R and Brand K. . 1993 Biochim Biophys. Acta 1176: 69–76.

  • Yamaguchi M, Hayashi Y and Matsukage A. . 1988 Nucl. Acids Res. 16: 8773–8787.

  • Yokoyama Y, Kawamoto T, Mitsuuchi Y, Kurosaki T, Toda K, Ushiro H, Terashima M, Sumimoto H, Kuribayashi I, Yamamoto Y, Maeda T, Ikeda H, Sagara Y and Shizuta Y. . 1990 Eur. J. Biochem. 194: 521–526.

  • Yee D, Favoni RE, Lebovic GS, Lombana F, Powel D, Reynolds CP and Rosen N. . 1990 J. Clin. Invest. 86: 1806–1814.

  • Zhang M, Maass N, Magit D and Sager R. . 1997 Cell Growth Diff. 8: 179–186.

Download references

Acknowledgements

Authors thank Dr P Ramsamooj for valuable discussions. Drs TS Papas and DK Watson are gratefully acknowledged for providing ETS1-expressing recombinant plasmids and Dr T Ogura for the pBal-CAT construct containing 5′ PARP from human leukocytes. This work was supported by grant PO1-CA74175 from the National Cancer Institute.

Author information

Authors and Affiliations

  1. Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Research Building, Room E215A, 3970 Reservoir Road, NW, Washington, 20007, DC, USA

    Viatcheslav A Soldatenkov, Amador Albor, Bharvin KR Patel, Roni Dreszer, Anatoly Dritschilo & Vicente Notario

Authors
  1. Viatcheslav A Soldatenkov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amador Albor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bharvin KR Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roni Dreszer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anatoly Dritschilo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vicente Notario
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Soldatenkov, V., Albor, A., Patel, B. et al. Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor. Oncogene 18, 3954–3962 (1999). https://doi.org/10.1038/sj.onc.1202778

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202778

Keywords

This article is cited by

Search

Advanced search

Quick links