Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

A role for Myc in facilitating transcription activation by E2F1

Abstract

Previous work has demonstrated that E2F proteins regulate the expression of various genes encoding proteins essential for DNA replication and cell-cycle progression. E2F1 in particular is required for the initial entry to the cell cycle from a quiescent state and is required for the activation of other E2F genes. Other work has demonstrated a role for the Myc transcription factor in the activation of a large number of genes associated with cell growth, including E2F genes. We now show that Myc is required to allow the interaction of the E2F1 protein with the E2F gene promoters. As such, Myc thus provides a link between the development of a growth-competent state during the initial stage of G1 and the activation of genes essential for DNA replication at G1/S.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Adams MR, Sears R, Nuckolls F, Leone G, Nevins JR . (2000). Complex transcriptional regulatory mechanisms control expression of the E2F3 locus. Mol Cell Biol 20: 3633–3639.

    Article  CAS  Google Scholar 

  • Bello-Fernandez C, Packham G, Cleveland JL . (1993). The ornithine decarboxylase gene is a transcriptional target of c-Myc. Proc Natl Acad Sci USA 90: 7804–7808.

    Article  CAS  Google Scholar 

  • Cole MD, McMahon SB . (1999). The Myc oncoprotein: a critical evaluation of transactivation and target gene regulation. Oncogene 18: 2916–2924.

    Article  CAS  Google Scholar 

  • DeGregori J, Kowalik T, Nevins JR . (1995). Cellular targets for activation by the E2F1 transcription factor include DNA synthesis and G1/S regulatory genes. Mol Cell Biol 15: 4215–4224.

    Article  CAS  Google Scholar 

  • Eisenman RN . (2001). Deconstructing Myc. Genes Dev 15: 2023–2030.

    Article  CAS  Google Scholar 

  • Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J et al. (2003). Genomic targets of the human c-Myc protein. Genes Dev 17: 1115–1129.

    Article  CAS  Google Scholar 

  • Frank SR, Schroeder M, Fernandez PC, Taubert S, Amati B . (2001). Binding of c-Myc to chromatin mediates mitogen-induced acetylation of histone H4 and gene activation. Genes Dev 15: 2069–2082.

    Article  CAS  Google Scholar 

  • Giangrande P, Zhu W, Rempel RE, Laakso N, Nevins JR . (2004). Combinatorial gene control involving E2F and E box family members. EMBO J 23: 1336–1347.

    Article  CAS  Google Scholar 

  • Giangrande PH, Hallstrom TC, Tunyaplin C, Calame K, Nevins JR . (2003). Identification of the E box factor TFE3 as a functional partner for the E2F3 transcription factor. Mol Cell Biol 23: 3707–3720.

    Article  CAS  Google Scholar 

  • Grandori C, Cowley SM, James LP, Eisenman RN . (2000). The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 16: 653–699.

    Article  CAS  Google Scholar 

  • Hallstrom TC, Nevins JR . (2003). Specificity in the activation and control of transcription factor E2F-dependent apoptosis. Proc Natl Acad Sci USA 100: 10848–10853.

    Article  CAS  Google Scholar 

  • He T-C, Zhou S, Da Costa LT, Yu J, Kinzler KW, Vogelstein B . (1998). A simplified system for generating recombinant adenoviruses. Biochem Biophys Res Commun 95: 2509–2514.

    CAS  Google Scholar 

  • Johnston LA, Prober DA, Edgar BA, Eisenman RN, Gallant P . (1999). Drosophila myc regulates cellular growth during development. Cell 98: 779–790.

    Article  CAS  Google Scholar 

  • Kong L-J, Chang JT, Bild AH, Nevins JR . (2007). Compensation and specificity of function within the E2F family. Oncogene 26: 321–327.

    Article  CAS  Google Scholar 

  • Leone G, DeGregori J, Sears R, Jakoi L, Nevins JR . (1997). Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F. Nature 387: 422–426.

    Article  CAS  Google Scholar 

  • Leone G, DeGregori J, Yan Z, Jakoi L, Ishida S, Williams RS et al. (1998). E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes Dev 12: 2120–2130.

    Article  CAS  Google Scholar 

  • Leone G, Sears R, Huang E, Rempel R, Nuckolls F, Park C-H et al. (2001). Myc requires distinct E2F activities to induce S phase and apoptosis. Mol Cell 8: 105–113.

    Article  CAS  Google Scholar 

  • Lin W-C, Lin F-T, Nevins JR . (2001). Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev 15: 1833–1845.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morita S, Kojima T, Kitamura T . (2000). Plat-E: an efficient and stable system for transient packaging of retroviruses. Gene Therapy 7: 1063–1066.

    Article  CAS  Google Scholar 

  • Orian A, van Steensel B, Delrow J, Bussemaker HJ, Li L, Sawado T et al. (2003). Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription network. Genes Dev 17: 1101–1114.

    Article  CAS  Google Scholar 

  • Sears R, Ohtani K, Nevins JR . (1997). Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals. Mol Cell Biol 17: 5227–5235.

    Article  CAS  Google Scholar 

  • Takahashi Y, Rayman JB, Dynlacht BD . (2000). Analysis of promoter binding by the E2F and Rb families in vivo: distinct E2F proteins mediate activation and repression. Genes Dev 14: 804–816.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Walker W, Zhou ZQ, Ota S, Wynshaw-Boris A, Hurlin PJ . (2005). Mnt-Max to Myc-Max complex switching regulates cell cycle entry. J Cell Biol 169: 405–413.

    Article  CAS  Google Scholar 

  • Wei C-L, Wu Q, Vega VB, Chiu KP, Ng P, Zhang T et al. (2006). A global map of p53 transcription factor binding sites in the human genome. Cell 124: 207–219.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J R Nevins.

Additional information

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leung, J., Ehmann, G., Giangrande, P. et al. A role for Myc in facilitating transcription activation by E2F1. Oncogene 27, 4172–4179 (2008). https://doi.org/10.1038/onc.2008.55

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2008.55

Keywords

This article is cited by

Search

Quick links