ZNF435, a Novel Human SCAN-containing Zinc Finger Protein, Inhibits AP-1-mediated Transcriptional Activation

  • Gu, Xing (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University) ;
  • Zheng, Mei (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University) ;
  • Fei, Xiangwei (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University) ;
  • Yang, Zhenxing (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University) ;
  • Li, Fan (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University) ;
  • Ji, Chaoneng (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University) ;
  • Xie, Yi (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University) ;
  • Mao, Yumin (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
  • Received : 2006.12.21
  • Accepted : 2007.02.23
  • Published : 2007.06.30

Abstract

Zinc finger transcription factor genes are a significant fraction of the genes in the vertebrate genome. Here we report the isolation and characterization of a human zinc finger-containing gene, ZNF435, from a fetal brain cDNA library. ZNF435 cDNA is 1290 base pairs in length and contains an open reading frame encoding 349 amino acids with four C2H2-type zinc fingers at its carboxyl terminus and a SCAN motif at its amino terminus. RT-PCR results showed that ZNF435 was expressed in all tested tissues. A ZNF435-GFP fusion protein was located in the nucleus and the four zinc fingers acted as nuclear localization signals (NLSs). ZNF435 was found to be capable of homo-association, and this effect was independent of its zinc fingers. Furthermore, ZNF435 proved to be a transcription repressor as its overexpression in AD293 cells inhibited the transcriptional activities of AP-1.

Keywords

Acknowledgement

Supported by : Nature Science Foundation of China

References

  1. Adachi, H. and Tsujimoto, M. (2002) Characterization of the human gene encoding the scavenger receptor expressed by endothelial cell and its regulation by a novel transcription factor, endothelial zinc finger protein-2. J. Biol. Chem. 277, 24014-24021 https://doi.org/10.1074/jbc.M201854200
  2. Adachi, M., Fukuda, M., and Nishida, E. (2000) Nuclear export of MAP kinase (ERK) involves a MAP kinase kinase (MEK)-dependent active transport mechanism. J. Cell Biol. 148, 849-856 https://doi.org/10.1083/jcb.148.5.849
  3. Attar, R. M. and Gilman, M. Z. (1992) Expression cloning of a novel zinc finger protein that binds to the c-fos serum response element. Mol. Cell. Biol. 12, 2432-2443 https://doi.org/10.1128/MCB.12.5.2432
  4. Barlow, P. N., Luisi, B., Milner, A., and Everett, R. (1994) Structure of the C3H4domain by H-nuclear magnetic resonance spectroscopy. A new structural class of zinc-finger. J. Mol. Biol. 237, 201-211 https://doi.org/10.1006/jmbi.1994.1222
  5. Borden, K. L. and Freemont, P. S. (1996) The RING finger domain: a recent example of a sequence-structure family. Curr. Opin. Struct. Biol. 6, 395-401 https://doi.org/10.1016/S0959-440X(96)80060-1
  6. Chang, L. and Karin, M. (2001) Mammalian MAP kinase signaling cascades. Nature 410, 211-218
  7. Collins, T., Stone, J. R., and Williams, A. J. (2001) All in the family: the BTB/POZ, KRAB, and SCAN domains. Mol. Cell. Biol. 21, 3609-3615 https://doi.org/10.1128/MCB.21.11.3609-3615.2001
  8. Edelstein, L. C. and Collins, T. (2005) The SCAN domain family of zinc finger transcription factors. Gene 359, 1-17 https://doi.org/10.1016/j.gene.2005.06.022
  9. Gonsky, R., Knauf, J. A., Elisei, R., Wang, J. W., Su, S., et al. (1997) Identification of rapid turnover transcripts overexpressed in thyroid tumors and thyroid cancer cell lines: use of a targeted differential RNA display method to select for mRNA subsets. Nucleic Acids Res. 25, 3823-3831 https://doi.org/10.1093/nar/25.19.3823
  10. Gou, D. M., Sun, Y., Gao, L., Chow, L. M., Huang, J., et al. (2001) Cloning and characterization of a novel Krüppel-like zinc finger gene, ZNF268, expressed in early human embryo. Biochim. Biophys. Acta 1518, 306-310 https://doi.org/10.1016/S0167-4781(01)00194-4
  11. Hammarstrom, A., Berndt, K. D., Sillard, R., Adermann, K., and Otting, G. (1996) Solution structure of a naturally-occurring zinc-peptide complex demonstrates that the N-terminal zincbinding module of the Lasp-1 LIM domain is an independent folding unit. Biochemistry 35, 12723-12732 https://doi.org/10.1021/bi961149j
  12. Han, Z. G., Zhang, Q. H., Ye, M., Kan, L. X., Gu, B. W., et al. (1999) Molecular cloning of six novel Krüppel-like zinc finger genes from hematopoietic cells and identification of a novel transregulator domain KRNB. J. Biol. Chem. 274, 35741-35748 https://doi.org/10.1074/jbc.274.50.35741
  13. Huang, X., Yuan, W., Huang, W., Bai, Y., Deng, Y., et al. (2006) ZNF569, a novel KRAB-containing zinc fnger protein, suppresses MAPK signaling pathway. Biochem. Biophys. Res. Commun. 346, 621-628 https://doi.org/10.1016/j.bbrc.2006.05.109
  14. Kort, E. N., Ballinger, D. G., Ding, W., Hunt, S. C., Bowen, B. R., et al. (2000) Evidence of linkage of familial hypoalphalipoproteinemia to a novel locus on chromosome 11q23. Am. J. Hum. Genet. 66, 1845-1856 https://doi.org/10.1086/302945
  15. Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zodv, M. C., et al. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860-921 https://doi.org/10.1038/35057062
  16. Lange, R., Christoph, A., Thiesen, H. J., Vopper, G., Johnson, K. R., et al. (1995) Developmentally regulated mouse gene NK10 encodes a zinc finger repressor with differential DNA binding domains. DNA Cell Biol. 14, 971-981 https://doi.org/10.1089/dna.1995.14.971
  17. Langmann, T., Schumacher, S. G., Morham, C., Honer, C., Heimerl, S., et al. (2003) ZNF202 is inversely regulated with its target genes ABCA1 and apoE during macrophage differenttiation and foam cell formation. J. Lipid Res. 44, 968-977 https://doi.org/10.1194/jlr.M300016-JLR200
  18. Lewis, T. S., Shapiro, P. S., and Ahn, N. G. (1998) Signal transduction through MAP kinase cascades. Adv. Cancer Res. 74, 49-139 https://doi.org/10.1016/S0065-230X(08)60765-4
  19. Li, Z., Wang, D., Na, X., Schoen, S. R., Messing, E. M., et al. (2003) The VHL protein recruits a novel KRAB-A domain protein to repress HIF-1alpha transcriptional activity. EMBO J. 22, 1857-1867 https://doi.org/10.1093/emboj/cdg173
  20. Liu, H., Zhu, C., Luo, J., Wang, Y., Li, D., et al. (2004) ZNF 411, a novel KRAB-containing zinc-fnger protein, suppresses MAP kinase signaling pathway. Biochem. Biophys. Res. Commun. 320, 45-53 https://doi.org/10.1016/j.bbrc.2004.05.130
  21. Lu, D., Searles, M. A., and Klug, A. (2003) Crystal structure of a zinc-finger-RNA complex reveals two modes of molecular recognition. Nature 426, 96-100 https://doi.org/10.1038/nature02088
  22. Luo, K., Yuan, J., Shan, Y., Li, J., Xu, M., et al. (2006) Activation of transcriptional activities of AP-1 and SRE by a novel zinc finger protein ZNF445. Gene 367, 89-100 https://doi.org/10.1016/j.gene.2005.09.023
  23. Noce, T., Fujiwara, Y., Sezaki, M., Fujimoto, H., and Higashinakagawa, T. (1992) Expression of a mouse zinc finger protein in both spermatocytes and oocytes during meiosis. Dev. Biol. 153, 356-367 https://doi.org/10.1016/0012-1606(92)90120-6
  24. Pavletich, N. P. and Pabo, C. O. (1991) Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science 252, 809-817 https://doi.org/10.1126/science.2028256
  25. Pengue, G., Calabro, V., Cannada-Bartoli, P., Pagliuca, A., and Lania, L. (1994) Repression of transcriptional activity at a distance by the evolutionarily conserved KRAB domain present in a subfamily of zinc finger proteins. Nucleic Acids Res. 22, 2908-2914 https://doi.org/10.1093/nar/22.15.2908
  26. Porsch-Ozcurumez, M., Langmann, T., Heimerl, S., Borsukova, H., Kaminski, W. E., et al. (2001) The zinc finger protein 202 (ZNF202) is a transcriptional repressor of ATP binding cassette transporter A1 (ABCA1) and ABCG1 gene expression and a modulator of cellular lipid efflux. J. Biol. Chem. 276, 12427-12433 https://doi.org/10.1074/jbc.M100218200
  27. Shapiro, M. B. and Senapathy, P. (1987) RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res. 15, 7155-7174 https://doi.org/10.1093/nar/15.17.7155
  28. Shaulian, E. and Karin, M. (2002) AP-1 as a regulator of cell life and death. Nat. Cell Biol. 4, E131-E136 https://doi.org/10.1038/ncb0502-e131
  29. Tara, L. S., Keith, F. S., Jenny, L. M., Paul, S., James, R. S., et al. (2003) The SCAN domain defines a large family of zinc finger transcription factors. Gene 310, 29-38 https://doi.org/10.1016/S0378-1119(03)00509-2
  30. 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
  31. Venter, J. C., Adam, M. D., Myers, E. W., Li, P. W., Mural, R. J., et al. (2001) The sequence of the human genome. Science 291, 1304-1351 https://doi.org/10.1126/science.1058040
  32. Wagner, S., Hess, M. A., Ormonde-Hanson, H., Malandro, J., Hu, H., et al. (2000) A broad role for the zinc finger protein ZNF202 in human lipid metabolism. J. Biol. Chem. 275, 15685-15690 https://doi.org/10.1074/jbc.M910152199
  33. Williams, A. J., Khachigian, L. M., and Collins, T. (1995) Isolation and characterization of a novel zinc-finger protein with transcriptional repressor activity. J. Biol. Chem. 270, 22143-22152 https://doi.org/10.1074/jbc.270.38.22143
  34. Wu, Y., Yu, L., Bi, G., Luo, K., Zhou, G., et al. (2003) Identification and characterization of two novel human SCAN domain-containing zinc finger genes ZNF396 and ZNF397. Gene 310, 193-201 https://doi.org/10.1016/S0378-1119(03)00551-1
  35. Yang, H., Yuan, W., Wang, Y., Zhu, C., Liu, B., et al. (2005) ZNF649, a novel Kruppel type zinc fnger protein, functions as a transcriptional suppressor. Biochem. Biophys. Res. Commun. 333, 206-215 https://doi.org/10.1016/j.bbrc.2005.05.101
  36. Yang, V. W. (1998) Eukaryotic transcription factors: identification, characterization and functions. J. Nutr. 128, 2045-2051 https://doi.org/10.1093/jn/128.11.2045