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Distinct Roles for JNK1 and JNK3 During TNF-α- or Etoposide-Induced Apoptosis in HeLa Cells

  • Ham, Young-Mi (Division of Pharmaceutical Biosciences, College of Pharmacy and the Research Institute for Pharmaceutical Sciences, Seoul National University) ;
  • Lim, Jin-Hee (Division of Pharmaceutical Biosciences, College of Pharmacy and the Research Institute for Pharmaceutical Sciences, Seoul National University) ;
  • Lee, Seung-Ki (Division of Pharmaceutical Biosciences, College of Pharmacy and the Research Institute for Pharmaceutical Sciences, Seoul National University)
  • Received : 2008.12.17
  • Accepted : 2009.10.12
  • Published : 2009.12.31

Abstract

Here, we show that JNK1 and JNK3 have different roles in ${\alpha}-$ or etoposide-induced apoptosis in HeLa cells. Dominant negative JNK1 inhibited $TNF-{\alpha}-$ or etoposide-induced apoptosis, while dominant negative JNK3 promoted $TNF-{\alpha}-$ or etoposide-induced apoptosis. During $TNF-{\alpha}$-induced apoptosis, JNK1 was activated in a biphasic manner, exhibiting both transient and sustained activity, whereas JNK3 was activated early and in a transient manner. The role of JNK3 activation was an anti-apoptotic effect, while the role of JNK1 activation was a pro-apoptotic effect. These results suggest that the anti-apoptotic mechanism of JNK3 in $TNF-{\alpha}$-induced apoptosis originates before the apoptotic machinery is triggered.

Keywords

Acknowledgement

Supported by : Ministry of Science and Technology, Korea Science and Engineering Foundation

References

  1. Chen, G., and Goeddel, D.V. (2002). TNF-R1 signaling: a beautiful pathway Science 296, 1634-1635 https://doi.org/10.1126/science.1071924
  2. Davis, R.J. (2000). Signal transduction by the JNK group of MAP kinases. Cell 103, 239-252 https://doi.org/10.1016/S0092-8674(00)00116-1
  3. Jurewicz, A., Matysiak, M., Tybor, K., and Selmaj, K. (2003). TNFinduced death of adult human oligodendrocytes is mediated by c-jun NH2-terminal kinase-3. Brain 126, 1358-1370 https://doi.org/10.1093/brain/awg146
  4. Kelliher, M.A., Grimm, S., Ishida, Y., Kuo, F., Stanger, B.Z., and Leder, P. (1998). The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity 8, 297-303 https://doi.org/10.1016/S1074-7613(00)80535-X
  5. Kennedy, N.J., and Davis, R.J. (2003). Role of JNK in tumor development. Cell Cycle 2, 199-201
  6. Kuan, C.Y., Whitmarsh, A.J., Yang, D.D., Liao, G., Schloemer, A.J., Dong, C., Bao, J., Banasiak, K.J., Haddad, G.G., Flavell, R.A., et al. (2003). A critical role of neural-specific JNK3 for ischemic apoptosis. Proc. Natl. Acad. Sci. USA 100, 15184-15189 https://doi.org/10.1073/pnas.2336254100
  7. Lamb, J.A., Ventura, J.J., Hess, P., Flavell, R.A., and Davis, R.J. (2003). JunD mediates survival signaling by the JNK signal transduction pathway. Mol. Cell 11, 1479-1489 https://doi.org/10.1016/S1097-2765(03)00203-X
  8. Li, B.S., Zhang, L., Takahashi, S., Ma, W., Jaffe, H., Kulkarni, A.B., and Pant, H.C. (2002). Cyclin-dependent kinase 5 prevents neuronal apoptosis by negative regulation of c-Jun N-terminal kinase 3. EMBO J. 21, 324-333 https://doi.org/10.1093/emboj/21.3.324
  9. Mielke, K., Damm, A., Yang, D.D., and Herdegen, T. (2000). Selective expression of JNK isoforms and stress-specific JNK activity in different neural cell lines. Mol. Brain Res. 75, 128-137 https://doi.org/10.1016/S0169-328X(99)00308-3
  10. Minden, A., Lin, A., McMahon, M., Lange-Carter, C., Derijard, B., Davis, R.J., Johnson, G.L., and Karin, M. (1994). Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science 266, 1719-1723 https://doi.org/10.1126/science.7992057
  11. Park, B.D., Ham, Y.M., Jeoung, H.J., Cho, S.J., Je, Y.T., Yoo, K.D., and Lee, S.K. (2007). Phosphorylation of Smac by JNK3 attenuates its interaction with XIAP. Biochem. Biophys. Res. Commun. 361, 994-999 https://doi.org/10.1016/j.bbrc.2007.07.121
  12. Sakon, S., Xue, X., Takekawa, M., Sasazuki, T., Okazaki, T., Kojima, Y., Piao, J.H., Yagita, H., Okumura, K., Doi, T., et al. (2003). NF-kappaB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J. 22, 3898-3909 https://doi.org/10.1093/emboj/cdg379
  13. Tang, F., Tang, G., Xiang, J., Dai, Q., Rosner, M.R., and Lin, A. (2002). Absence of NF-κB-mediated inhibition of c-Jun Nterminal kinase activation contributes to tumor necrosis factor a induced apoptosis. Mol. Cell. Biol. 22, 8571-8579 https://doi.org/10.1128/MCB.22.24.8571-8579.2002
  14. Varfolomeev, E.E., and Ashkenazi, A. (2004). Tumor necrosis factor: an apoptosis JuNKie? Cell 116, 491-497 https://doi.org/10.1016/S0092-8674(04)00166-7
  15. Varfolomeev, E.E., Schuchmann, M., Luria, V., Chiannilkulchai, N., Beckmann, J.S., Mett, I.L., Rebrikov, D., Brodianski, V.M., Kemper, O.C., Kollet, O., et al. (1998). Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9, 267-276 https://doi.org/10.1016/S1074-7613(00)80609-3
  16. Weston, C.R., and Davis R.J. (2007). The JNK signal transduction pathway. Curr. Opin. Cell Biol. 19, 142-149 https://doi.org/10.1016/j.ceb.2007.02.001
  17. Yeh, W.C., Shahinian, A., Speiser, D., Kraunus, J., Billia, F., Wakeham, A.A., de la Pompa, J.L., Ferrick, D., Hum, B., Iscove, N., et al. (1997). Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2- deficient mice. Immunity 7, 715-725 https://doi.org/10.1016/S1074-7613(00)80391-X
  18. Yeh, J.H., Hsu, S.C., Han, S.H., and Lai, M.Z. (1998). Mitogenactivated protein kinase kinase antagonized fas-associated death domain protein-mediated apoptosis by induced FLICEinhibitory protein expression. J. Exp. Med. 188, 1795-1802 https://doi.org/10.1084/jem.188.10.1795

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