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A novel human KRAB-related zinc finger gene ZNF425 inhibits mitogen-activated protein kinase signaling pathway

  • Wang, Yuequn (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Ye, Xiangli (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Zhou, Junmei (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Wan, Yongqi (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Xie, Huaping (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Deng, Yun (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Yan, Yan (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Li, Yongqing (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Fan, Xiongwei (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Yuan, Wuzhou (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Mo, Xiaoyang (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Wu, Xiushan (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University)
  • Received : 2010.09.28
  • Accepted : 2010.12.06
  • Published : 2011.01.31

Abstract

Zinc finger (ZNF) proteins play a critical role in cell growth, proliferation, apoptosis, and intracellular signal transduction. In this paper, we cloned and characterized a novel human KRAB-related zinc finger gene, ZNF425, which encodes a protein of 752 amino acids. ZNF425 is strongly expressed in the three month old human embryos and then is almost undetectable in six month old embryos and in adult tissues. An EGFP-ZNF425 fusion protein can be found in both the nucleus and the cytoplasm. ZNF425 appears to act as a transcription repressor. Over-expression of ZNF425 inhibits the transcriptional activities of SRE, AP-1, and SRF. Deletion analysis indicates that the C2H2 domain is the main region responsible for the repression. Our results suggest that the ZNF425 gene is a new transcriptional inhibitor that functions in the MAPK signaling pathway.

Keywords

References

  1. Klug, A. and Schwabe, J. W. R. (1995) Protein motifs 5. Zinc fingers. FASEB J. 9, 597-604. https://doi.org/10.1096/fasebj.9.8.7768350
  2. Brayer, K. J. and Segal, D. J. (2008) Keep your fingers off my DNA: protein-protein interactions mediated by C2H2 zinc finger domains. Cell Biochem. Biophys. 50, 111-131. https://doi.org/10.1007/s12013-008-9008-5
  3. Krishna, S. S., Majumdar, I. and Grishin, N. V. (2003) Structural classification of zinc fingers: survey and summary. Nucleic. Acids. Res. 31, 532-550. https://doi.org/10.1093/nar/gkg161
  4. Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K. and Doyle, M. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860-921. https://doi.org/10.1038/35057062
  5. Nolte, R. T., Conlin, R. M., Harrison, S. C. and Brown, R. S. (1998) Differing roles for zinc finger in DNA recognition: structure of a six-finger transcription factor IIIA complex. Proc. Natl. Acad. Sci. 95, 2938-2943. https://doi.org/10.1073/pnas.95.6.2938
  6. Cao, L., Wang, Z., Zhu, C., Zhao, Y., Yuan, W., Li, J., Wang, Y., Ying, Z., Li, Y., Yu, W., Wu, X. and Liu, M. (2005) ZNF383, a novel KRAB-containing zinc finger protein, suppresses MAPK signaling pathway. Biochem. Biophys. Res. Commun. 333, 1050-1059. https://doi.org/10.1016/j.bbrc.2005.05.193
  7. Nancy, F., Qian, Z., Kathleen, G., Cheol, Y. C., Yongsok, K. and Robert, A. S. (2000) The multitype zinc-finger protein U-shaped functions in heart cell specification in the Drosophila embryo. Proc. Natl. Acad. Sci. U.S.A. 97, 7348-7353. https://doi.org/10.1073/pnas.97.13.7348
  8. Chang, L. and Karin, M. (2001) Mammalian MAP kinase signaling cascades. Nature 410, 37-40. https://doi.org/10.1038/35065000
  9. Treisman, R. (1996) Regulation of transcription by MAP kinase cascades. Curr. Opin. Cell Biol. 8, 205-215. https://doi.org/10.1016/S0955-0674(96)80067-6
  10. Looman, C., Abrink, M., Mark, C. and Hellman, L. (2002) KRAB zinc finger proteins: an analysis of the molecular mechanisms governing their increase in numbers an complexity during evolution. Mol. Biol. Evol. 19, 2118-2130. https://doi.org/10.1093/oxfordjournals.molbev.a004037
  11. Margolin, J. F., Friedman, J. R., Meyer, W. K. H., Vissing, H., Thiesen, H. J. and Rauscher, F. J. (1994) Kruppel-associated boxes are potent transcriptional repression domains. Proc. Natl. Acad. Sci. U.S.A. 91, 4509-4513. https://doi.org/10.1073/pnas.91.10.4509
  12. Bellefroid, E. J., Poncelet, D. A., Lecocq, P. J., Revelant, O. and Martial, J. A. (1991) The evolutionarily conserved Kruppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc. Natl. Acad. Sci. U.S.A. 88, 3608-3612. https://doi.org/10.1073/pnas.88.9.3608
  13. Luo, K., Wang, Y., Zhu, C., Li, Y., Wang, Y., Jiao, W., Liu, M. and Wu, X. (2002) Expression of a novel Kruppel-like zinc finger gene, ZNF382, in human heart. Biochem. Biophys. Res. Comm. 299, 606-612. https://doi.org/10.1016/S0006-291X(02)02700-6
  14. Yi, F., Li, Y., Ma, W., Li, D., Zhu, C., Luo, J., Wang, Y., Huang, X., Yuan, W., Liu, M. and Wu, X. (2004) A novel KRAB zinc-finger protein, ZNF480, expresses in human heart and activates transcriptional activities of AP-1 and SRE. Biochem. Biophys. Res. Commun. 320, 409-415. https://doi.org/10.1016/j.bbrc.2004.05.182
  15. Huang, X., Yuan, W., Huang, W., Bai, Y., Deng, Y., Zhu, C., Liang, P., Li, Y., Du, X., Liu. M., Wang, Y. and Wu, X. (2006) ZNF569, a novel KRAB-containing zinc finger protein, suppresses MAPK signaling pathway. Biochem. Biophys. Res. Commun. 346, 621-628. https://doi.org/10.1016/j.bbrc.2006.05.109
  16. Li, Y., Yang, D., Bai, Y., Mo, X., Huang, W., Yuan, W., Yin, Z., Deng, Y., Murashko, O., Wang, Y., Fan, X., Zhu, C., Ocorr, K., Bodmer, R. and Wu, X. (2008) ZNF418, a novel human KRAB/C2H2 zinc finger protein, suppresses MAPK signaling pathway. Mol. Cell Biochem. 310, 141-151. https://doi.org/10.1007/s11010-007-9674-4
  17. Cheng, Y., Geng, H., Cheng, S., Liang, P., Bai, Y., Li, J., Srivastava, G., Ng, M., Fukagawa, T., Wu, X., Chan, T. C. and Tao, Q. (2010) The KRAB Zinc finger protein ZNF382 is a general, pro-apoptotic tumor suppressor repressing multiple oncogenes and frequently silenced by CpG methylation in multiple carcinomas. Cancer Res. 70, 6516-6526. https://doi.org/10.1158/0008-5472.CAN-09-4566
  18. Wang, Y., Zhou, J., Ye, X., Wan, Y., Li, Y., Mo, X., Yuan, W., Yan, Y., Luo, N., Wang, Z., Fan, X., Deng, Y. and Wu X. (2010) ZNF424, a novel human KRAB/C2H2 zinc finger protein, suppresses NFAT and p21 pathway. BMB Rep. 43, 212-218. https://doi.org/10.5483/BMBRep.2010.43.3.212
  19. Shaknovich, R., Yeyati, P. L., Ivins, S., Melnick, A., Lempert, C., Waxman, S., Zelent, A., and Licht. J. D. (1998) The promyelocytic leukemia zinc finger protein affects myeloid cell growth, differentiation, and apoptosis. Mol. Cell. Biol. 18, 5533-5545.
  20. Wu, X. (2006a) Introduction to Heart Development. Science Publishing House, Beijing, China
  21. Wu, X. (2006b) Signal Pathways and Heart Development. Huaxuegongye Publishing House, Beijing, China
  22. Whitmarsh, A. J. and Davis, R. J. (2000) Regulation of transcription factor function by phosphorylation. Cell. Mol. Life Sci. 45, 1172-1183.
  23. Kim, S. S., Chen, Y. M., Leary, E. O., Witzgall, R., Vidal, M. and Bonventre, J. V. (1996) A novel member of the RING finger family, KRIP-1, associated with the KRAB-A transcriptional repressor domain of zinc finger proteins. Proc. Natl. Acad. Sci. U.S.A. 93, 5299-15304.
  24. Parlakian, A , Tuil, D., Hamard, G., Tavernier, G., Hentzen, D., Concordet, J. P., Paulin, D., Li, Z. and Daegelen, D. (2004) Targeted inactivation of serum response factor in the developing heart results in myocardial defects and embryonic lethality. Mol. Cell Biol. 24, 5281-5289. https://doi.org/10.1128/MCB.24.12.5281-5289.2004
  25. Miano, J. M., Ramanan, N., Georger, M. A., de Nesy Bentley, K. L., Emerson, R. L., Balza, R. O., Jr Xiao, Q., Weiler, H., Ginty, D. and Misra, R. P. (2004) Restricted inactivation of serum response factor to the cardiovascular system. Proc. Nat. Acad. Sci. U.S.A. 101, 17132-17137. https://doi.org/10.1073/pnas.0406041101
  26. Freire, G., Ocampo, C., Ilbawi, N., Griffin, A. J. and Gupta, M. (2007) Overt expression of AP-1 reduces alpha myosin heavy chain expression and contributes to heart failure from chronic volume overload. J. Mol. Cell. Cardiol. 43, 465-478. https://doi.org/10.1016/j.yjmcc.2007.07.046
  27. Herrera, R. E., Shaw, P. E. and Nordheim, A. (1989) Occupation of the c-fos serum response element by a multi-protein complex is unaltered by growth-factor induction. Nature 340, 68-70. https://doi.org/10.1038/340068a0
  28. Wang, Y., Luo, K., Li, Y., Zhu, C. and Wu, X. (2001) A rapid method of extracting total RNA from embryo tissues. Life Sci. Res. 5, 88-90.

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