C-Myc Transrepression and Cell Transformation

  • L. A. Lee
  • C. V. Dang
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 224)


The c-Myc oncoprotein affects cell differentiation, cell proliferation, apoptosis, and cell transformation. Many studies have ultimately centered on the ability of c-Myc to transactivate through the E-box as the mechanism underlying all of these Myc functions. It is so widely accepted that c-Myc transactivation is necessary for cell transformation, that the authentication of putative target genes requires the presence of E-boxes within these genes that can be transactivated by c-Myc in transient transfection assays. However, several examples exist where mutations of c-Myc result in the disassociation of c-Myc transformation from transactivation, suggesting the existence of other mechanisms that confer its transforming properties. Recently, c-Myc mediated transrepression, a poorly understood function of c-Myc, has been the focus of increased interest as several genes have been reported to be down-regulated by c-Myc. Evidence now suggests that transrepression may contribute to cell transformation.


Cell Transformation Transactivation Domain Putative Target Gene Transient Transfection Assay Initiator Element 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Tikhonenko, A., D. Black, and M. Linial. 1996. In press.Google Scholar
  2. 2.
    Inghirami, G., F. Grignani, L. Sternas, L. Lombardi, D. M. Knowles, and R. Dalla-Favera. 1990. Down-regulation of LFA-1 adhesion receptors by c-myc oncogene in human B lymphoblastoid cells. Science 250:682–686.PubMedCrossRefGoogle Scholar
  3. 3.
    Akeson, R., and R. Bernards. 1990. N-myc down regulates neural cell adhesion molecule expression in rat neuroblastoma. Mol Cell Biol 10:2012–2016.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Yang, B.-S., T. J. Geddes, R. J. Pogulis, B. de Crombrugghe, and S. O. Freytag. 1991. Transcriptional suppression of cellular gene expression by c-Myc. Mol Cell Biol 11:2291–2295.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Antonsen, P., M. Pray, A. Jacobsson, and G. Xanthopoulos. 1995. Myc inhibits CCAAT/enhancer-binding protein alph-gene expression in HIB-1B hibernoma cells through interactions with the core promoter region. Eur J Biochem 232:397–403.CrossRefGoogle Scholar
  6. 6.
    Christy, R., K. Kastner, D. Geiman, and M. Lane. 1991. CCAATT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3–L1 preadipocytes. Proc Natl Acad Sci USA 88:2593–2597.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Suen, T.-C, and M.-C. Hung. 1991. c-myc reverses neu-induced transformation morphology by transcriptional repression. Mol Cell Biol 11:354–362.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Kaddurah-Daouk, R., J. M. Greene, A. S. Baldwin Jr., and R. E. Kingston. 1987. Activation and repression of mammalian gene expression by the c-myc protein. Genes Dev 1:347–357.PubMedCrossRefGoogle Scholar
  9. 9.
    Ziff, E. B., and R. M. Evans. 1978. Cell 14:1463–1475.CrossRefGoogle Scholar
  10. 10.
    Versteeg, R., I. Noordermeer, M. Kruse-Wolters, D. Ruiter, and P. Schrier. 1988. c-myc down-regulates class I HLA expression in human melanomas. EMBO J 7:1023–1029.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Van Antwerp, M. E., D. G. Chen, C. Chang, and E. V. Prochownik. 1992. A point mutation in the MyoD basic domain imparts c-Myc-like properties. Proc Natl Acad Sci USA 89:9010–9014.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Lee, L. A., C. Dolde, J. Barrett, C. S. Wu, and C. V. Dang. 1996. A link between c-Myc-mediated transcriptional repression and neoplastic transformation. J Clin Invest 97:1687–1695.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Roy, A. L., C. Carruthers, T. Gutjahr, and R. G. Roeder. 1993. Direct role for Myc in transcription initiation mediated by interactions with TFII-I. Nature 365:359–361.PubMedCrossRefGoogle Scholar
  14. 14.
    Hernandez, N. 1993. TBP, a universal eukaryotic transcription factor? Genes Dev 7:1291–1308.PubMedCrossRefGoogle Scholar
  15. 15.
    Smale, S. T., and D. Baltimore. 1989. The “initiator” as a transcription control element. Cell 57:103–113.PubMedCrossRefGoogle Scholar
  16. 16.
    Li, L.-H., C. Nerlov, G. Prendergast, D. MacGregor, and E. B. Ziff. 1994. c-Myc represses transcription in vivo by a novel mechanism dependent on the initiator element and Myc box II. EMBO J 13:4010–4079.Google Scholar
  17. 17.
    Mai, S., and I.-L. Mårtensson. 1995. The c-myc protein represses λ5 and TdT initiators. Nuc Acids Res 23:1–9.CrossRefGoogle Scholar
  18. 18.
    Yano, T., C. Sander, H. Clark, M. Dolezal, E. Jaffe, and M. Raffeld. 1993. Clustered mutations in the second exon of the MYC gene in sporadic Burkitt’s lymphoma. Oncogene 8:2741–2748.PubMedGoogle Scholar
  19. 19.
    Raffeld, M., T. Yano, A. T. Hoang, B. Lewis, H. M. Clark, T. Otsuki, and C. V. Dang. 1995. Clustered Mutations in the transcriptional activation domain of Myc in 8q24 translocated lymphomas and their functional consequences. Curr Top Microbiol Immunol. 194:265–72.PubMedGoogle Scholar
  20. 20.
    Clark, H. M., T. Yano, T. Otsuki, E. S. Jaffe, D. Shibata, and M. Raffeld. 1994. Mutations in the coding region of c-MYC in AIDS-associated and other aggressive lymphomas. Cancer Res 54:3383–3386.PubMedGoogle Scholar
  21. 21.
    Brough, D., T. Hofmann, K. Ellwood, R. Townley, and M. Cole. 1995. An essential domain of the c-Myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation. Mol Cell Biol 15:1536–1544.PubMedCentralPubMedGoogle Scholar
  22. 22.
    Yang, B., J. Gilbert, and S. Freytag. 1993. Overexpression of myc suppresses CCAAT transcription factor/nuclear factor 1–dependent promoters in vivo. Mol Cell Biol 13:3093–3102.PubMedCentralPubMedGoogle Scholar
  23. 23.
    Lenardo, M., A. Rustgi, A. Schievella, and R. Bernards. 1989. Suppression of MHC class 1 gene expression by N-myc through enhancer inactivation. EMBO J 8:3351–3355.PubMedCentralPubMedGoogle Scholar
  24. 24.
    van’t Veer, L., R. Beijersbergen, and R. Bernards. 1993. N-myc suppresses major histocompatibility complex Class I gene expression through down-regulation of the p50 subunit of NF-kB. EMBO J 12:195–200.PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • L. A. Lee
    • 1
  • C. V. Dang
    • 2
  1. 1.Department of Medicine, The Johns HopkinsUniversity School of MedicineBaltimoreUSA
  2. 2.The Johns Hopkins Oncology Center, The Johns HopkinsUniversity School of MedicineBaltimoreUSA

Personalised recommendations