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JNK2 Participates in Spindle Assembly during Mouse Oocyte Meiotic Maturation

  • Xin Huang (a1) (a2), Jing-Shan Tong (a2), Zhen-Bo Wang (a2), Cai-Rong Yang (a2), Shu-Tao Qi (a2), Lei Guo (a2), Ying-Chun Ouyang (a2), Song Quan (a3), Qing-Yuan Sun (a2), Zhong-Quan Qi (a1), Ru-Xin Huang (a1) (a4) and Hai-Long Wang (a1)...


It is well known that c-Jun N-terminal kinase (JNK) plays pivotal roles in various mitotic events, but its function in mammalian oocyte meiosis remains unknown. In this study, we found that no specific JNK2 signal was detected in germinal vesicle stage. JNK2 was associated with the spindles especially the spindle poles and cytoplasmic microtubule organizing centers at prometaphase I, metaphase I, and metaphase II stages. JNK2 became diffusely distributed and associated with the midbody at telophase I stage. Injection of myc-tagged JNK2α1 mRNA into oocytes also revealed its localization on spindle poles. The association of JNK2 with spindle poles was further confirmed by colocalization with the centrosomal proteins, γ-tubulin and Plk1. Nocodazole treatment showed that JNK2 may interact with Plk1 to regulate the spindle assembly. Then we investigated the possible function of JNK2 by JNK2 antibody microinjection and JNK specific inhibitor SP600125 treatment. These two manipulations caused abnormal spindle formation and decreased the rate of first polar body (PB1) extrusion. In addition, inhibition of JNK2 resulted in impaired localization of Plk1. Taken together, our results suggest that JNK2 plays an important role in spindle assembly and PB1 extrusion during mouse oocyte meiotic maturation.


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Bagowski, C.P., Xiong, W. & Ferrell, J.E. Jr. (2001). c-Jun N-terminal kinase activation in Xenopus laevis eggs and embryos. A possible non-genomic role for the JNK signaling pathway. J Biol Chem 276(2), 14591465.
Bode, A.M. & Dong, Z. (2007). The functional contrariety of JNK. Mol Carcinog 46(8), 591598.
Brennan, I.M., Peters, U., Kapoor, T.M. & Straight, A.F. (2007). Polo-like kinase controls vertebrate spindle elongation and cytokinesis. PLoS One 2(5), e409.
Chang, L., Jones, Y., Ellisman, M.H., Goldstein, L.S. & Karin, M. (2003). JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev Cell 4(4), 521533.
Dai, W., Wang, Q. & Traganos, F. (2002). Polo-like kinases and centrosome regulation. Oncogene 21(40), 61956200.
Daire, V., Giustiniani, J., Leroy-Gori, I., Quesnoit, M., Drevensek, S., Dimitrov, A., Perez, F. & Pous, C. (2009). Kinesin-1 regulates microtubule dynamics via a c-Jun N-terminal kinase-dependent mechanism. J Biol Chem 284(46), 3199232001.
Gupta, S., Barrett, T., Whitmarsh, A.J., Cavanagh, J., Sluss, H.K., Derijard, B. & Davis, R.J. (1996). Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 15(11), 27602770.
Gutierrez, G.J., Tsuji, T., Cross, J.V., Davis, R.J., Templeton, D.J., Jiang, W. & Ronai, Z.A. (2010). JNK-mediated phosphorylation of Cdc25C regulates cell cycle entry and G(2)/M DNA damage checkpoint. J Biol Chem 285(19), 1421714228.
Ho, C.Y. & Li, H.Y. (2010). DNA damage during mitosis invokes a JNK-mediated stress response that leads to cell death. J Cell Biochem 110(3), 725731.
Horiuchi, D., Barkus, R.V., Pilling, A.D., Gassman, A. & Saxton, W.M. (2005). APLIP1, a kinesin binding JIP-1/JNK scaffold protein, influences the axonal transport of both vesicles and mitochondria in Drosophila. Curr Biol 15(23), 21372141.
Inamura, N., Enokido, Y. & Hatanaka, H. (2001). Involvement of c-Jun N-terminal kinase and caspase 3-like protease in DNA damage-induced, p53-mediated apoptosis of cultured mouse cerebellar granule neurons. Brain Res 904(2), 270278.
Jacobs-Helber, S.M. & Sawyer, S.T. (2004). Jun N-terminal kinase promotes proliferation of immature erythroid cells and erythropoietin-dependent cell lines. Blood 104(3), 696703.
Karsenti, E. & Vernos, I. (2001). The mitotic spindle: A self-made machine. Science 294(5542), 543547.
Kawauchi, T., Chihama, K., Nabeshima, Y. & Hoshino, M. (2003). The in vivo roles of STEF/Tiam1, Rac1 and JNK in cortical neuronal migration. EMBO J 22(16), 41904201.
Kyriakis, J.M. & Avruch, J. (2001). Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81(2), 807869.
LaRosa, C. & Downs, S.M. (2007). Meiotic induction by heat stress in mouse oocytes: Involvement of AMP-activated protein kinase and MAPK family members. Biol Reprod 76(3), 476486.
Levy, J.R. & Holzbaur, E.L. (2006). Cytoplasmic dynein/dynactin function and dysfunction in motor neurons. Int J Dev Neurosci 24(2–3), 103111.
Li, C., Ge, B., Nicotra, M., Stern, J.N., Kopcow, H.D., Chen, X. & Strominger, J.L. (2008). JNK MAP kinase activation is required for MTOC and granule polarization in NKG2D-mediated NK cell cytotoxicity. Proc Natl Acad Sci USA 105(8), 30173022.
Li, S., Ou, X.H., Wang, Z.B., Xiong, B., Tong, J.S., Wei, L., Li, M., Yuan, J., Ouyang, Y.C., Hou, Y., Schatten, H. & Sun, Q.Y. (2010). ERK3 is required for metaphase-anaphase transition in mouse oocyte meiosis. PLoS One 5(9).
MacCorkle, R.A. & Tan, T.H. (2004). Inhibition of JNK2 disrupts anaphase and produces aneuploidy in mammalian cells. J Biol Chem 279(38), 4011240121.
MacCorkle-Chosnek, R.A., VanHooser, A., Goodrich, D.W., Brinkley, B.R. & Tan, T.H. (2001). Cell cycle regulation of c-Jun N-terminal kinase activity at the centrosomes. Biochem Biophys Res Commun 289(1), 173180.
Matsumura, S., Toyoshima, F. & Nishida, E. (2007). Polo-like kinase 1 facilitates chromosome alignment during prometaphase through BubR1. J Biol Chem 282(20), 1521715227.
Mingo-Sion, A.M., Marietta, P.M., Koller, E., Wolf, D.M. & Van Den Berg, C.L. (2004). Inhibition of JNK reduces G2/M transit independent of p53, leading to endoreduplication, decreased proliferation, and apoptosis in breast cancer cells. Oncogene 23(2), 596604.
Mood, K., Bong, Y.S., Lee, H.S., Ishimura, A. & Daar, I.O. (2004). Contribution of JNK, Mek, Mos and PI-3K signaling to GVBD in Xenopus oocytes. Cell Signal 16(5), 631642.
Moon, D.O., Kim, M.O., Kang, C.H., Lee, J.D., Choi, Y.H. & Kim, G.Y. (2009). JNK inhibitor SP600125 promotes the formation of polymerized tubulin, leading to G2/M phase arrest, endoreduplication, and delayed apoptosis. Exp Mol Med 41(9), 665677.
Nomachi, A., Nishita, M., Inaba, D., Enomoto, M., Hamasaki, M. & Minami, Y. (2008). Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A. J Biol Chem 283(41), 2797327981.
Sabapathy, K. & Wagner, E.F. (2004). JNK2: A negative regulator of cellular proliferation. Cell Cycle 3(12), 15201523.
Schuh, M. & Ellenberg, J. (2007). Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. Cell 130(3), 484498.
Steigemann, P. & Gerlich, D.W. (2009). Cytokinetic abscission: Cellular dynamics at the midbody. Trends Cell Biol 19(11), 606616.
Sun, Q.Y. & Schatten, H. (2006). Role of NuMA in vertebrate cells: Review of an intriguing multifunctional protein. Front Biosci 11, 11371146.
Sun, S.C., Wei, L., Li, M., Lin, S.L., Xu, B.Z., Liang, X.W., Kim, N.H., Schatten, H., Lu, S.S. & Sun, Q.Y. (2009). Perturbation of survivin expression affects chromosome alignment and spindle checkpoint in mouse oocyte meiotic maturation. Cell Cycle 8(20), 33653372.
Teraishi, F., Wu, S., Sasaki, J., Zhang, L., Davis, J.J., Guo, W., Dong, F. & Fang, B. (2005). JNK1-dependent antimitotic activity of thiazolidin compounds in human non-small-cell lung and colon cancer cells. Cell Mol Life Sci 62(19–20), 23822389.
Tong, C., Fan, H.Y., Lian, L., Li, S.W., Chen, D.Y., Schatten, H. & Sun, Q.Y. (2002). Polo-like kinase-1 is a pivotal regulator of microtubule assembly during mouse oocyte meiotic maturation, fertilization, and early embryonic mitosis. Biol Reprod 67(2), 546554.
Tseng, C.J., Wang, Y.J., Liang, Y.C., Jeng, J.H., Lee, W.S., Lin, J.K., Chen, C.H., Liu, I.C. & Ho, Y.S. (2002). Microtubule damaging agents induce apoptosis in HL 60 cells and G2/M cell cycle arrest in HT 29 cells. Toxicology 175(1–3), 123142.
Ventura, J.J., Cogswell, P., Flavell, R.A., Baldwin, A.S. Jr. & Davis, R.J. (2004). JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species. Genes Dev 18(23), 29052915.
Vogt, E., Kirsch-Volders, M., Parry, J. & Eichenlaub-Ritter, U. (2008). Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error. Mutat Res 651(1–2), 1429.
Wang, I.C., Chen, Y.J., Hughes, D.E., Ackerson, T., Major, M.L., Kalinichenko, V.V., Costa, R.H., Raychaudhuri, P., Tyner, A.L. & Lau, L.F. (2008). FoxM1 regulates transcription of JNK1 to promote the G1/S transition and tumor cell invasiveness. J Biol Chem 283(30), 2077020778.
Weston, C.R. & Davis, R.J. (2007). The JNK signal transduction pathway. Curr Opin Cell Biol 19(2), 142149.
Xiao, D., Pinto, J.T., Soh, J.W., Deguchi, A., Gundersen, G.G., Palazzo, A.F., Yoon, J.T., Shirin, H. & Weinstein, I.B. (2003). Induction of apoptosis by the garlic-derived compound S-allylmercaptocysteine (SAMC) is associated with microtubule depolymerization and c-Jun NH(2)-terminal kinase 1 activation. Cancer Res 63(20), 68256837.
Xiong, B., Li, S., Ai, J.S., Yin, S., Ouyang, Y.C., Sun, S.C., Chen, D.Y. & Sun, Q.Y. (2008a). BRCA1 is required for meiotic spindle assembly and spindle assembly checkpoint activation in mouse oocytes. Biol Reprod 79(4), 718726.
Xiong, B., Sun, S.C., Lin, S.L., Li, M., Xu, B.Z., OuYang, Y.C., Hou, Y., Chen, D.Y. & Sun, Q.Y. (2008b). Involvement of Polo-like kinase 1 in MEK1/2-regulated spindle formation during mouse oocyte meiosis. Cell Cycle 7(12), 18041809.
Xiong, B., Yu, L.Z., Wang, Q., Ai, J.S., Yin, S., Liu, J.H., OuYang, Y.C., Hou, Y., Chen, D.Y., Zou, H. & Sun, Q.Y. (2007). Regulation of intracellular MEK1/2 translocation in mouse oocytes: Cytoplasmic dynein/dynactin-mediated poleward transport and cyclin B degradation-dependent release from spindle poles. Cell Cycle 6(12), 15211527.
Yang, D.D., Conze, D., Whitmarsh, A.J., Barrett, T., Davis, R.J., Rincon, M. & Flavell, R.A. (1998). Differentiation of CD4+ T cells to Th1 cells requires MAP kinase JNK2. Immunity 9(4), 575585.
Yu, L.Z., Xiong, B., Gao, W.X., Wang, C.M., Zhong, Z.S., Huo, L.J., Wang, Q., Hou, Y., Liu, K., Liu, X.J., Schatten, H., Chen, D.Y. & Sun, Q.Y. (2007). MEK1/2 regulates microtubule organization, spindle pole tethering and asymmetric division during mouse oocyte meiotic maturation. Cell Cycle 6(3), 330338.
Zhang, D., Yin, S., Jiang, M.X., Ma, W., Hou, Y., Liang, C.G., Yu, L.Z., Wang, W.H. & Sun, Q.Y. (2007). Cytoplasmic dynein participates in meiotic checkpoint inactivation in mouse oocytes by transporting cytoplasmic mitotic arrest-deficient (Mad) proteins from kinetochores to spindle poles. Reproduction 133(4), 685695.
Zhang, H., Shi, X., Zhang, Q.J., Hampong, M., Paddon, H., Wahyuningsih, D. & Pelech, S. (2002). Nocodazole-induced p53-dependent c-Jun N-terminal kinase activation reduces apoptosis in human colon carcinoma HCT116 cells. J Biol Chem 277(46), 4364843658.


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JNK2 Participates in Spindle Assembly during Mouse Oocyte Meiotic Maturation

  • Xin Huang (a1) (a2), Jing-Shan Tong (a2), Zhen-Bo Wang (a2), Cai-Rong Yang (a2), Shu-Tao Qi (a2), Lei Guo (a2), Ying-Chun Ouyang (a2), Song Quan (a3), Qing-Yuan Sun (a2), Zhong-Quan Qi (a1), Ru-Xin Huang (a1) (a4) and Hai-Long Wang (a1)...


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