Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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DNAJB9 Inhibits p53-Dependent Oncogene-Induced Senescence and Induces Cell Transformation

  • Lee, Hyeon Ju (Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine) ;
  • Jung, Yu-Jin (Department of Biological Sciences, Kangwon National University) ;
  • Lee, Seungkoo (Department of Anatomic Pathology, Kangwon National University School of Medicine, Kangwon National University Hospital) ;
  • Kim, Jong-Il (Genomic Medicine Institute, Medical Research Center, Seoul National University) ;
  • Han, Jeong A. (Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine)
  • Received : 2019.10.11
  • Accepted : 2020.02.26
  • Published : 2020.04.30
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Abstract

DNAJB9 is known to be a member of the molecular chaperone gene family, whose cellular function has not yet been fully characterized. Here, we investigated the cellular function of DNAJB9 under strong mitogenic signals. We found that DNAJB9 inhibits p53-dependent oncogene-induced senescence (OIS) and induces neoplastic transformation under oncogenic RAS activation in mouse primary fibroblasts. In addition, we observed that DNAJB9 interacts physically with p53 under oncogenic RAS activation and that the p53-interacting region of DNAJB9 is critical for the inhibition of p53-dependent OIS and induction of neoplastic transformation by DNAJB9. These results suggest that DNAJB9 induces cell transformation under strong mitogenic signals, which is attributable to the inhibition of p53-dependent OIS by physical interactions with p53. This study might contribute to our understanding of the cellular function of DNAJB9 and the molecular basis of cell transformation.

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References

  1. Ahn, B.Y., Trinh, D.L., Zajchowski, L.D., Lee, B., Elwi, A.N., and Kim, S.W. (2010). Tid1 is a new regulator of p53 mitochondrial translocation and apoptosis in cancer. Oncogene 29, 1155-1166. https://doi.org/10.1038/onc.2009.413
  2. Akagi, T. (2004). Oncogenic transformation of human cells: shortcomings of rodent model systems. Trends Mol. Med. 10, 542-548. https://doi.org/10.1016/j.molmed.2004.09.001
  3. Awe, K., Lambert, C., and Prange, R. (2008). Mammalian BiP controls posttranslational ER translocation of the hepatitis B virus large envelope protein. FEBS lett. 582, 3179-3184. https://doi.org/10.1016/j.febslet.2008.07.062
  4. Bartkova, J., Horejsi, Z., Koed, K., Kramer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J.M., Lukas, C., et al. (2005). DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434, 864-870. https://doi.org/10.1038/nature03482
  5. Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L.V., Kolettas, E., Niforou, K., Zoumpourlis, V.C., et al. (2006). Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444, 633-637. https://doi.org/10.1038/nature05268
  6. Benanti, J.A. and Galloway, D.A. (2004). Normal human fibroblasts are resistant to RAS-induced senescence. Mol. Cell. Biol. 24, 2842-2852. https://doi.org/10.1128/MCB.24.7.2842-2852.2004
  7. Campisi, J. and d'Adda di Fagagna, F. (2007). Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8, 729-740. https://doi.org/10.1038/nrm2233
  8. Cerami, E., Gao, J., Dogrusoz, U., Gross, B.E., Sumer, S.O., Aksoy, B.A., Jacobsen, A., Byrne, C.J., Heuer, M.L., Larsson, E., et al. (2012). The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401-404. https://doi.org/10.1158/2159-8290.CD-12-0095
  9. Choi, E.M., Kim, S.R., Lee, E.J., and Han, J.A. (2009). Cyclooxygenase-2 functionally inactivates p53 through a physical interaction with p53. Biochim. Biophys. Acta 1793, 1354-1365. https://doi.org/10.1016/j.bbamcr.2009.05.006
  10. Courtois-Cox, S., Jones, S.L., and Cichowski, K. (2008). Many roads lead to oncogene-induced senescence. Oncogene 27, 2801-2809. https://doi.org/10.1038/sj.onc.1210950
  11. Di Micco, R., Fumagalli, M., Cicalese, A., Piccinin, S., Gasparini, P., Luise, C., Schurra, C., Garre, M., Nuciforo, P.G., Bensimon, A., et al. (2006). Oncogeneinduced senescence is a DNA damage response triggered by DNA hyperreplication. Nature 444, 638-642. https://doi.org/10.1038/nature05327
  12. Di Micco, R., Fumagalli, M., and d'Adda di Fagagna, F. (2007). Breaking news: high-speed race ends in arrest--how oncogenes induce senescence. Trends Cell Biol. 17, 529-536. https://doi.org/10.1016/j.tcb.2007.07.012
  13. Dimri, G.P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E.E., Linskens, M., Rubelj, I., Pereira-Smith, O., et al. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. U. S. A. 92, 9363-9367. https://doi.org/10.1073/pnas.92.20.9363
  14. Ferbeyre, G., de Stanchina, E., Lin, A.W., Querido, E., McCurrach, M.E., Hannon, G.J., and Lowe, S.W. (2002). Oncogenic ras and p53 cooperate to induce cellular senescence. Mol. Cell. Biol. 22, 3497-3508. https://doi.org/10.1128/MCB.22.10.3497-3508.2002
  15. Gao, J., Aksoy, B.A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S.O., Sun, Y., Jacobsen, A., Sinha, R., Larsson, E., et al. (2013). Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal. 6, pl1.
  16. Halazonetis, T.D., Gorgoulis, V.G., and Bartek, J. (2008). An oncogeneinduced DNA damage model for cancer development. Science 319, 1352-1355. https://doi.org/10.1126/science.1140735
  17. Hanahan, D. and Weinberg, R.A. (2000). The hallmarks of cancer. Cell 100, 57-70. https://doi.org/10.1016/S0092-8674(00)81683-9
  18. Hanahan, D. and Weinberg, R.A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674. https://doi.org/10.1016/j.cell.2011.02.013
  19. Hartl, F.U., Bracher, A., and Hayer-Hartl, M. (2011). Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332. https://doi.org/10.1038/nature10317
  20. Jozefczuk, J., Drews, K., and Adjaye, J. (2012). Preparation of mouse embryonic fibroblast cells suitable for culturing human embryonic and induced pluripotent stem cells. J. Vis. Exp. 64, 3854.
  21. Kang, T.W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011). Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479, 547-551. https://doi.org/10.1038/nature10599
  22. Kim, S.R., Park, J.H., Lee, M.E., Park, J.S., Park, S.C., and Han, J.A. (2008). Selective COX-2 inhibitors modulate cellular senescence in human dermal fibroblasts in a catalytic activity-independent manner. Mech. Ageing Dev. 129, 706-713. https://doi.org/10.1016/j.mad.2008.09.003
  23. Kuk, M.U., Kim, J.W., Lee, Y.S., Cho, K.A., Park, J.T., and Park, S.C. (2019). Alleviation of senescence via ATM inhibition in accelerated aging models. Mol. Cells 42, 210-217. https://doi.org/10.14348/molcells.2018.0352
  24. Kurisu, J., Honma, A., Miyajima, H., Kondo, S., Okumura, M., and Imaizumi, K. (2003). MDG1/ERdj4, an ER-resident DnaJ family member, suppresses cell death induced by ER stress. Genes Cells 8, 189-202. https://doi.org/10.1046/j.1365-2443.2003.00625.x
  25. Lee, H.J., Kim, J.M., Kim, K.H., Heo, J.I., Kwak, S.J., and Han, J.A. (2015). Genotoxic stress/p53-induced DNAJB9 inhibits the pro-apoptotic function of p53. Cell Death Differ. 22, 86-95. https://doi.org/10.1038/cdd.2014.116
  26. Nardella, C., Clohessy, J.G., Alimonti, A., and Pandolfi, P.P. (2011). Prosenescence therapy for cancer treatment. Nat. Rev. Cancer 11, 503-511. https://doi.org/10.1038/nrc3057
  27. Narita, M., Nunez, S., Heard, E., Narita, M., Lin, A.W., Hearn, S.A., Spector, D.L., Hannon, G.J., and Lowe, S.W. (2003). Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113, 703-716. https://doi.org/10.1016/S0092-8674(03)00401-X
  28. Ory, D.S., Neugeboren, B.A., and Mulligan, R.C. (1996). A stable humanderived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes. Proc. Natl. Acad. Sci. U. S. A. 93, 11400-11406. https://doi.org/10.1073/pnas.93.21.11400
  29. Qiu, X.B., Shao, Y.M., Miao, S., and Wang, L. (2006). The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell. Mol. Life Sci. 63, 2560-2570. https://doi.org/10.1007/s00018-006-6192-6
  30. Sarkisian, C.J., Keister, B.A., Stairs, D.B., Boxer, R.B., Moody, S.E., and Chodosh, L.A. (2007). Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis. Nat. Cell Biol. 9, 493-505. https://doi.org/10.1038/ncb1567
  31. Serrano, M., Lin, A.W., McCurrach, M.E., Beach, D., and Lowe, S.W. (1997). Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593-602. https://doi.org/10.1016/S0092-8674(00)81902-9
  32. Shen, Y., Meunier, L., and Hendershot, L.M. (2002). Identification and characterization of a novel endoplasmic reticulum (ER) DnaJ homologue, which stimulates ATPase activity of BiP in vitro and is induced by ER stress. J. Biol. Chem. 277, 15947-15956. https://doi.org/10.1074/jbc.M112214200
  33. Tomayko, M.M. and Reynolds, C.P. (1989). Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother. Pharmacol. 24, 148-154. https://doi.org/10.1007/BF00300234
  34. Trinh, D.L., Elwi, A.N., and Kim, S.W. (2010). Direct interaction between p53 and Tid1 proteins affects p53 mitochondrial localization and apoptosis. Oncotarget 1, 396-404. https://doi.org/10.18632/oncotarget.174
  35. Vos, M.J., Hageman, J., Carra, S., and Kampinga, H.H. (2008). Structural and functional diversities between members of the human HSPB, HSPH, HSPA, and DNAJ chaperone families. Biochemistry 47, 7001-7011. https://doi.org/10.1021/bi800639z
  36. Walsh, P., Bursac, D., Law, Y.C., Cyr, D., and Lithgow, T. (2004). The J-protein family: modulating protein assembly, disassembly and translocation. EMBO Rep. 5, 567-571. https://doi.org/10.1038/sj.embor.7400172
  37. Zhao, J.J., Roberts, T.M., and Hahn, W.C. (2004). Functional genetics and experimental models of human cancer. Trends Mol. Med. 10, 344-350. https://doi.org/10.1016/j.molmed.2004.05.005

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