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Cisplatin-induced apoptotic endonuclease EndoG inhibits telomerase activity and causes malignant transformation of human CD4+ T lymphocytes

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Aims and scope Submit manuscript

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Abstract

Alternative splicing of telomerase catalytic subunit hTERT pre-mRNA (human Telomerase Reverse Transcriptase) regulates telomerase activity. Increased expression of non-active splice variant hTERT results in inhibition of telomerase. Apoptotic endonuclease EndoG is known to participate in hTERT alternative splicing. Expression of EndoG can be induced in response to DNA damages. The aim of this study was to determine the ability of a DNA-damaging compound, cisplatin, to induce EndoG and its influence on alternative splicing of hTERT and telomerase activity in human CD4+ Т lymphocytes. Overexpression of EndoG in CD4+ T cells downregulated expression of the active full-length hTERT variant and upregulated its non-active spliced variant. Reduction of full-length hTERT caused downregulation of telomerase activity, shortening of telomeres length during cell divisions, converting cells to the replicative senescence state, activation of apoptosis and finally cell death. Few cells survived and underwent malignant transformation. Transformed cells have increased telomerase activity and proliferative potential compare to initial CD4+ T cells. These cells have phenotype of T lymphoblastic leukemic cells and are able to form tumors and cause death in experimental mice.

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References

  1. Shay, J.W., Clin. Cancer Res., 2003, vol. 9, pp. 3521–3525.

    CAS  Google Scholar 

  2. Harley, C.B., Futcher, A.B., and Greider, C.W., Nature, 1990, vol. 345, pp. 458–460. doi 10.1038/345458?0

    Article  CAS  Google Scholar 

  3. Wright, W.E., Pereira-Smith, O.M., and Shay, J.W., Mol. Cell Biol., 1989, vol. 9, pp. 3088–3092.

    Article  CAS  Google Scholar 

  4. Hanahan, D. and Weinberg, R.A., Cell, 2000, vol. 100, pp. 57–70.

    Article  CAS  Google Scholar 

  5. Kim, N.W., Piatyszek, M.A., Prowse, K.R., Harley, C.B., West, M.D., Ho, P.L., Coviello, G.M., Wright, W.E., Weinrich, S.L., and Shay, J.W., Science, 1994, vol. 266, pp. 2011–2015.

    Article  CAS  Google Scholar 

  6. Marian, C.O., Wright, W.E., and Shay, J.W., Int. J. Cancer, 2010, vol. 127, pp. 321–331. doi 10.1002/ijc.25043

    CAS  Google Scholar 

  7. Marian, C.O., Cho, S.K., McEllin, B.M., Maher, E.A., Hatanpaa, K.J., Madden, C.J., Mickey, B.E., Wright, W.E., Shay, J.W., and Bachoo, R.M., Clin. Cancer Res., 2010, vol. 16, pp. 154–163. doi 10.1158/1078-0432.CCR-09-2850

    Article  CAS  Google Scholar 

  8. Blackburn, E.H., Nature, 2000, vol. 408, pp. 53–56. doi 10.1038/35040500

    Article  CAS  Google Scholar 

  9. Meyerson, M., Counter, C.M., Eaton, E.N., Ellisen, L.W., Steiner, P., Caddle, S.D., Ziaugra, L., Beijersbergen, R.L., Davidoff, M.J., Liu, Q., Bacchetti, S., Haber, D.A., and Weinberg, R.A., Cell, 1997, vol. 90, pp. 785–795.

    Article  CAS  Google Scholar 

  10. Saeboe-Larssen, S., Fossberg, E., and Gaudernack, G., BMC Mol. Biol., 2006, vol. 7, p. 26. doi 10.1186/1471-2199-7-26

  11. Ulaner, G.A., Hu, J.F., Vu, T.H., Oruganti, H., Giudice, L.C., and Hoffman, A.R., Int. J. Cancer, 2000, vol. 85, pp. 330–335.

    Article  CAS  Google Scholar 

  12. Ulaner, G.A., Hu, J.F., Vu, T.H., Giudice, L.C., and Hoffman, A.R., Cancer Res., 1998, vol. 58, pp. 4168–4172.

    CAS  Google Scholar 

  13. Listerman, I., Sun, J., Gazzaniga, F.S., Lukas, J.L., and Blackburn, E.H., Cancer Res., 2013, vol. 73, pp. 2817–2828. doi 10.1158/0008-5472.CAN-12-3082

    Article  CAS  Google Scholar 

  14. Zhdanov, D.D., Vasina, D.A., Orlova, V.S., Gotovtseva, V.Y., Bibikova, M.V., Pokrovsky, V.S., Pokrovskaya, M.V., Aleksandrova, S.S., and Sokolov, N.N., Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 2016, vol. 10, pp. 310–321.

    Article  Google Scholar 

  15. Nagata, S., Nagase, H., Kawane, K., Mukae, N., and Fukuyama, H., Cell Death Diff., 2003, vol. 10, pp. 108–116. doi 10.1038/sj.cdd.4401161

    Article  CAS  Google Scholar 

  16. Ruiz-Carrillo, A. and Renaud, J., EMBO J., 1987, vol. 6, pp. 401–407.

    CAS  Google Scholar 

  17. Yin, X., Apostolov, E.O., Shah, S.V., Wang, X., Bogdanov, K.V., Buzder, T., Stewart, A.G., and Basnakian, A.G., JASN, 2007, vol. 18, pp. 2544–2553. doi 10.1681/ASN.2006080896

    Article  CAS  Google Scholar 

  18. Chan, F.K.-M., Moriwaki, K., and De Rosa, M.J., Methods Mol. Biol., 2013, vol. 979, pp. 65–70. doi 10.1007/978-1-62703-290-2_7

    Article  CAS  Google Scholar 

  19. Basnakian, A.G., Apostolov, E.O., Yin, X., Abiri, S.O., Stewart, A.G., Singh, A.B., and Shah, S.V., Exp. Cell Res., 2006, vol. 312, pp. 4139–4149. doi 10.1016/j.yexcr.2006.09.012

    Article  CAS  Google Scholar 

  20. Laemmli, U.K., Nature, 1970, vol. 227, pp. 680–685.

    Article  CAS  Google Scholar 

  21. Hofnagel, O., Luechtenborg, B., Stolle, K., Lorkowski, S., Eschert, H., Plenz, G., and Robenek, H., Arter. Thromb. Vasc. Biol., 2004, vol. 24, pp. 1789–1795. doi 10.1161/01.ATV.0000140061.89096.2b

    Article  CAS  Google Scholar 

  22. Kovalenko, N.A., Zhdanov, D.D., Bibikova, M.V., and Gotovtseva, V.Y., Biochemistry (Moscow) Supplement. Series B: Biomedical Chemistry, 2012, vol. 6, pp. 48–54.

    Article  Google Scholar 

  23. O’Callaghan, N.J. and Fenech, M., Biological Procedures Online, 2011, vol. 13. p. 3. doi 10.1186/1480-9222-13-3

  24. Cawthon, R.M., Nucleic Acids Research, 2002, vol. 30, e47.

    Article  Google Scholar 

  25. Darzynkiewicz, Z., Galkowski, D., and Zhao, H., Methods, 2008, vol. 44, pp. 250–254. doi 10.1016/j.ymeth.2007.11.08

    Article  CAS  Google Scholar 

  26. Pokrovsky, V.S., Treshalina, H.M., Lukasheva, E.V., Sedakova, L.A., Medentzev, A.G., Arinbasarova, A.Y., and Berezov, T.T., Anti-Cancer Drugs, 2013, vol. 24, pp. 846–851. doi 10.1097/CAD.0b013ee328362fbe2

    Article  CAS  Google Scholar 

  27. Ruden, M. and Puri, N., Cancer Treat. Rev., 2013, vol. 39, pp. 444–456. doi 10.1016/j.ctrv.2012.06.007

    Article  CAS  Google Scholar 

  28. Scovassi, A.I. and Torriglia, A., Eur. J. Histochem., 2003, vol. 47, pp. 185–194.

    Article  CAS  Google Scholar 

  29. Effros, R.B. and Pawelec, G., Immunology Today, 1997, vol. 18, pp. 450–454.

    Article  CAS  Google Scholar 

  30. Counter, C.M., Gupta, J., Harley, C.B., Leber, B., and Bacchetti, S., Blood, 1995, vol. 85, pp. 2315–2320.

    CAS  Google Scholar 

  31. Moro-García, M.A., Alonso-Arias, R., and López-Larrea, C., Cur. Genomics, 2012, vol. 13, pp. 589–602. doi 10.2174/138920212803759749

    Article  Google Scholar 

  32. Hodes, R.J., Hathcock, K.S., and Weng, N., Nat. Rev. Immunol., 2002, vol. 2, pp. 699–706. doi 10.1038/nri890

    Article  CAS  Google Scholar 

  33. Read, M.A., Wood, A.A., Harrison, J.R., Gowan, S.M., Kelland, L.R., Dosanjh, H.S., and Neidle, S., J. Med. Chem., 1999, vol. 42, pp. 4538–4546.

    Article  CAS  Google Scholar 

  34. Zhou, Z., Du, Y., Zhang, L., and Dong, S., Biosens. Bioelectron., 2012, vol. 34, pp. 100–105. doi 10.1016/j.bios.2012.01.024

    Article  CAS  Google Scholar 

  35. Martadinata, H., Heddi, B., Lim, K.W., and Phan, A.T., Biochemistry, 2011, vol. 50, pp. 6455–6461. doi 10.1021/bi200569f

    Article  CAS  Google Scholar 

  36. Zhdanov, D.D., Fahmi, T., Wang, X., Apostolov, E.O., Sokolov, N.N., Javadov, S., and Basnakian, A.G., DNA and Cell Biology, 2015, vol. 34, pp. 316–326. doi 10.1089/dna.2014.2772

    Article  CAS  Google Scholar 

  37. Sangle, N.A., Agarwal, A.M., Smock, K.J., Leavitt, M.O., Warnke, R., Bahler, D., and Perkins, S.L., App. Immunohistochem. Mol. Morphol., 2011, vol. 19, pp. 579–583. doi 10.1097/PAI.0b013e318221c672

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Biomedical Chemistry, ul. Pogodinskaya 10, Moscow, 119121, Russia

    D. D. Zhdanov, V. S. Pokrovsky, M. V. Pokrovskaya, S. S. Aleksandrova & N. N. Sokolov

  2. Ecological Faculty, Peoples Friendship University of Russia, ul. Miklukho-Маklaya 6, Moscow, 117198, Russia

    D. D. Zhdanov, D. A. Vasina, V. S. Orlova & V. S. Pokrovsky

  3. Institute of Theoretical and Experimental Biophysics, ul. Institutskaya 3, Puschino, Moscow region, 142290, Russia

    E. V. Orlova

Authors
  1. D. D. Zhdanov
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  2. D. A. Vasina
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  3. E. V. Orlova
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  4. V. S. Orlova
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  5. V. S. Pokrovsky
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  6. M. V. Pokrovskaya
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  7. S. S. Aleksandrova
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  8. N. N. Sokolov
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Correspondence to D. D. Zhdanov.

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Original Russian Text © D.D. Zhdanov, D.A. Vasina, E.V. Orlova, V.S. Orlova, V.S. Pokrovsky, M.V. Pokrovskaya, S.S. Aleksandrova, N.N. Sokolov, 2017, published in Biomeditsinskaya Khimiya.

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Zhdanov, D.D., Vasina, D.A., Orlova, E.V. et al. Cisplatin-induced apoptotic endonuclease EndoG inhibits telomerase activity and causes malignant transformation of human CD4+ T lymphocytes. Biochem. Moscow Suppl. Ser. B 11, 251–264 (2017). https://doi.org/10.1134/S199075081703012X

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  • DOI: https://doi.org/10.1134/S199075081703012X

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