Skip to main content
Log in

A novel zinc-finger protein ZNF436 suppresses transcriptional activities of AP-1 and SRE

  • Original Paper
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Mitogen-activated protein kinases (MAPKs) are evolutionary conserved enzymes in cell signal transduction connecting cell-surface receptors to critical regulatory targets within cells and control cell survival, adaptation, and proliferation. Previous studies revealed that zinc finger proteins are involved in the regulation of the MAPK signaling pathways. Here we report the identification and characterization of a novel human zinc finger protein, ZNF436. The cDNA of ZNF436 is 3.8 kb, encoding 470 amino acids in the nucleus. The protein is highly conserved in evolution across different vertebrate species from rat to human. RT-PCR indicates that ZNF436 is expressed in all the human fetal tissues examined, with a high level in brain and heart. Overexpression of pCMV-tag2A-ZNF436 in the COS-7 cells represses the transcriptional activities of SRE and AP-1. These results suggest that ZNF436 is a member of the zinc finger transcription factor family and may act as a negative regulator in gene transcription mediated by the MAPK signaling pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

DMEM:

Dulbecco’s Modified Eagle Medium

DAPI4’:

6′-Diamidino-2- phenylindole hydrochloride

MAPK:

Mitogen-activated protein kinase

MAPKKMKK or MEK:

MAPK kinase

MAPKKK or MEKKA:

MAPKK kinase or MEK kinase

SRE:

Serum response element

AP-1:

Activation protein 1

References

  1. Tjian R, Maniatis T (1994) Transcriptional activation: a complex puzzle with few easy pieces. Cell 77(1):5–8

    Article  PubMed  CAS  Google Scholar 

  2. Maldonado E, Hampsey M, Reinberg D (1999) Repression: targeting the heart of the matter. Cell 99(5):455–458

    Article  PubMed  CAS  Google Scholar 

  3. Park M, Wu X, Golden K, Axelrod JD, Bodmer R (1996) The wingless signaling pathway is directly involved in Drosophila heart development. Dev Biol 177(1):104–116

    Article  PubMed  CAS  Google Scholar 

  4. Pavletich NP, Pabo CO (1993) Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. Science 261(5129):1701–1707

    Article  PubMed  CAS  Google Scholar 

  5. Venter JC, Adams MD, Myers EW, Li PW et al (2001) The sequence of the human genome. Science 291(5507):1304–1351

    Article  PubMed  CAS  Google Scholar 

  6. Huang C, Wang Y, Li D, Li Y, Luo J, Yuan W, Ou Y, Zhu C, Zhang Y, Wang Z, Liu M Wu X (2004) Inhibition of transcriptional activities of AP-1 and c-Jun by a new zinc finger protein ZNF394. Biochem Biophys Res Commun 320(4):1298–1305

    Article  PubMed  CAS  Google Scholar 

  7. Hagen G, Muller S, Beato M, Suske G (1994) Sp1-mediated transcriptional activation is repressed by Sp3. EMBO J 13(16):3843–3851

    PubMed  CAS  Google Scholar 

  8. Drummond IA, Madden SL, Rohwer-Nutter P, Bell GI, Sukhatme VP, Rauscher FJ 3rd (1992) Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1. Science 257(5070):674–678

    Article  PubMed  CAS  Google Scholar 

  9. Schuh R, Aicher W, Gaul U, Cote S, Preiss A, Maier D, Seifert E, Nauber U, Schroder C, Kemler R et al (1986) A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Kruppel, a Drosophila segmentation gene. Cell 47(6):1025–1032

    Article  PubMed  CAS  Google Scholar 

  10. Kadonaga JT, Carner KR, Masiarz FR, Tjian R (1987) Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell 51(6):1079–1090

    Article  PubMed  CAS  Google Scholar 

  11. Haber DA, Buckler AJ, Glaser T, Call KM, Pelletier J, Sohn RL, Douglass EC, Housman DE (1990) An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor. Cell 61(7):1257–1269

    Article  PubMed  CAS  Google Scholar 

  12. Vortkamp A, Gessler M, Grzeschik KH (1991) GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families. Nature 352(6335):539–540

    Article  PubMed  CAS  Google Scholar 

  13. Dang DT, Pevsner J, Yang VW (2000) The biology of the mammalian Kruppel-like family of transcription factors. Int J Biochem Cell Biol 32(11–12):1103–1121

    Article  PubMed  CAS  Google Scholar 

  14. Wu LC (2002) ZAS: C2H2 zinc finger proteins involved in growth and development. Gene Exp 10(4):137–152

    CAS  Google Scholar 

  15. Takeuchi A, Mishina Y, Miyaishi O, Kojima E, Hasegawa T Isobe K (2003) Heterozygosity with respect to Zfp148 causes complete loss of fetal germ cells during mouse embryogenesis. Nat Genet 33(2):172–176

    Article  PubMed  CAS  Google Scholar 

  16. Turner J, Crossley M (1999) Mammalian Kruppel-like transcription factors: more than just a pretty finger. Trends Biochem Sci 24(6):236–240

    Article  PubMed  CAS  Google Scholar 

  17. Villavicencio EH, Walterhouse DO, Iannaccone PM (2000) The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet 67(5):1047–1054

    PubMed  CAS  Google Scholar 

  18. Li Y, Wang Y, Zhang C, Yuan W, Wang J, Zhu C, Chen L, Huang W, Zeng W, Wu X, Liu M (2004) ZNF322, a novel human C2H2 Kruppel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways. Biochem Biophys Res Commun 325(4):1383–1392

    Article  PubMed  CAS  Google Scholar 

  19. Davis RJ (1994) MAPKs: new JNK expands the group. Trends Biochem Sci 19(11):470–473

    Article  PubMed  CAS  Google Scholar 

  20. Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410(6824):37–40

    Article  PubMed  CAS  Google Scholar 

  21. English J, Pearson G, Wilsbacher J, Swantek J, Karandikar M, Xu S, Cobb MH (1999) New insights into the control of MAP kinase pathways. Exp Cell Res 253(1):255–270

    Article  PubMed  CAS  Google Scholar 

  22. Davis RJ (1993) The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 268(20):14553–14556

    PubMed  CAS  Google Scholar 

  23. Sanchez I, Hughes RT, Mayer BJ, Yee K, Woodgett JR, Avruch J, Kyriakis JM, Zon LI (1994) Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature 372(6508):794–798

    PubMed  CAS  Google Scholar 

  24. Gupta S, Campbell D, Derijard B, Davis RJ (1995) Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 267(5196):389–393

    Article  PubMed  CAS  Google Scholar 

  25. Mavrothalassitis G, Ghysdael J (2000) Proteins of the ETS family with transcriptional repressor activity. Oncogene 19(55):6524–6532

    Article  PubMed  CAS  Google Scholar 

  26. Jeanmougin F, Thompson JD, Gouy M, Higgins DG, Gibson TJ (1998) Multiple sequence alignment with Clustal X. Trends Biochem Sci 23(10):403–405

    Article  PubMed  CAS  Google Scholar 

  27. Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81(2):807–869

    PubMed  CAS  Google Scholar 

  28. Keeton AB, Bortoff KD, Bennett WL, Franklin JL, Venable DY Messina JL (2003) Insulin-regulated expression of Egr-1 and Krox20: dependence on ERK1/2 and interaction with p38 and PI3-kinase pathways. Endocrinology 144(12):5402–5410

    Article  PubMed  CAS  Google Scholar 

  29. Ray A, Yu GY, Ray BK (2002) Cytokine-responsive induction of SAF-1 activity is mediated by a mitogen-activated protein kinase signaling pathway. Mol Cell Biol 22(4):1027–1035

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to all members of the Center for Heart Development, College of Life Sciences in Hunan Normal University for their excellent technical assistance and encouragement. This study was supported in part by the National Natural Science Foundation of China (No. 90508004, 30470867, 30270722, 30570934, 30571048, 30570265), PCSIRT of Education Ministry of China (IRT0445), National Basic Research Program of China (2005CB522505), and the Foundation of Hunan Province (No. 04FJ2006).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Chuanbing Zhu or Xiushan Wu.

Additional information

Yongqing Li and Xiaoyan Du contributed equally to the work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, Y., Du, X., Li, F. et al. A novel zinc-finger protein ZNF436 suppresses transcriptional activities of AP-1 and SRE. Mol Biol Rep 33, 287–294 (2006). https://doi.org/10.1007/s11033-006-9019-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-006-9019-5

Keywords

Navigation