E2F1: Transcriptional Machinery in Colon Cancer

  • I. Vasavi
  • A. M. V. N. Prathyusha
  • Malothu Ramesh
  • K. Satish Kumar
  • B. Pratap Naidu
  • Pallaval Veera BramhachariEmail author
  • N. M. Yugandhar
  • P. Rama Chandra Ganesh


E2F family of transcription factor acts as central modulator for important cellular events including cell cycle progression, apoptosis, and DNA damage response. E2F1 regulates G1/S-phase transition of cell cycle transactivating a variety of genes involved in chromosomal DNA replication, including its own promoter. E2F1 is regulated in a cell cycle-dependent manner, principally through its temporal association with pocket protein family member, retinoblastoma. Pocket proteins, in turn, regulated through phosphorylation by cyclin-dependent kinase (CDK). Different E2F family exhibits distinct cell cycle and apoptotic activities. This review focuses on E2F1 function and its putative role in colon cancer.


E2F1 Colon cancer Retinoblastoma (RB) CDK 


  1. 1.
    Arnold, M., Sierra, M. S., Laversanne, M., Soerjomataram, I., Jemal, A., Bray, F. (2016).Global patterns and trends in colorectal cancer incidence and mortality. Gut, gutjnl-2015CrossRefPubMedGoogle Scholar
  2. 2.
    Banerjee, D., Gorlick, R., Liefshitz, A., Danenberg, K., Danenberg, P. C., Danenberg, P. V., ... Kemeny, N. (2000). Levels of E2F-1 expression are higher in lung metastasis of colon cancer as compared with hepatic metastasis and correlate with levels of thymidylate synthase. Cancer Res 60(9):2365–2367Google Scholar
  3. 3.
    Cecchini MJ, Dick FA (2011) The biochemical basis of CDK phosphorylation-independent regulation of E2F1 by the retinoblastoma protein. Biochem J 434(2):297–308CrossRefPubMedGoogle Scholar
  4. 4.
    Chen C, Wells AD (2007) Comparative analysis of E2F family member oncogenic activity. PLoS One 2(9):e912CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Chen M, Capps C, Willerson JT, Zoldhelyi P (2002) E2F-1 regulates nuclear factor-κB activity and cell adhesion. Circulation 106(21):2707–2713CrossRefPubMedGoogle Scholar
  6. 6.
    Denchi EL, Helin K (2005) E2F1 is crucial for E2F-dependent apoptosis. EMBO Rep 6(7):661–668CrossRefGoogle Scholar
  7. 7.
    Dimova DK, Dyson NJ (2005) The E2F transcriptional network: old acquaintances with new faces. Oncogene 24(17):2810–2826CrossRefPubMedGoogle Scholar
  8. 8.
    Elliott MJ, Dong YB, Yang H, McMasters KM (2001) E2F-1 up-regulates c-myc and p14arf and induces apoptosis in colon cancer cells. Clin Cancer Res 7(11):3590–3597PubMedGoogle Scholar
  9. 9.
    Engelmann, D., Mayoli-Nüssle, D., Mayrhofer, C., Fürst, K., Alla, V., Stoll, A., ... Pützer, B. M. (2013). E2F1 promotes angiogenesis through the VEGF-C/VEGFR-3 axis in a feedback loop for cooperative induction of PDGF-B. J Mol Cell Biol, mjt035Google Scholar
  10. 10.
    Fang Z, Gong C, Liu H, Zhang X, Mei L, Song M et al (2015) E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2. Biochem Biophys Res Commun 464(2):407–415CrossRefPubMedGoogle Scholar
  11. 11.
    Fontemaggi G, Dell’Orso S, Trisciuoglio D, Shay T, Melucci E, Fazi F et al (2009) The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis. Nat Struct Mol Biol 16(10):1086–1093CrossRefPubMedGoogle Scholar
  12. 12.
    Hershko T, Ginsberg D (2004) Up-regulation of Bcl-2 homology 3 (BH3)-only proteins by E2F1 mediates apoptosis. J Biol Chem 279(10):8627–8634CrossRefPubMedGoogle Scholar
  13. 13.
    Irwin, M., Marin, M. C., Phillips, A. C., Seelan, R. S., Smith, D. I., Liu, W., ... Kaelin Jr, W. G. (2000). Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature 407(6804):645–648CrossRefGoogle Scholar
  14. 14.
    Iwamoto, M., Banerjee, D., Menon, L. G., Jurkiewicz, A., Rao, P. H., Kemeny, N. E., ... Bertino, J. R. (2004). Overexpression of E2F-1 in lung and liver metastases of human colon cancer is associated with gene amplification. Cancer Biol Ther 3(4):395–399CrossRefGoogle Scholar
  15. 15.
    Julian LM, Palander O, Seifried LA, Foster JEG, Dick FA (2008) Characterization of an E2F1-specific binding domain in pRB and its implications for apoptotic regulation. Oncogene 27(11):1572–1579CrossRefPubMedGoogle Scholar
  16. 16.
    Kofunato, Y., Kumamoto, K., Saitou, K., Hayase, S., Okayama, H., Miyamoto, K., ... Koyama, Y. (2012). UHRF1 expression is up regulated and associated with cellular proliferation in colorectal cancer. Oncol Rep 28(6):1997–2002CrossRefPubMedGoogle Scholar
  17. 17.
    Pillai S, Kovacs M, Chellappan S (2010) Regulation of vascular endothelial growth factor receptors by Rb and E2F1: role of acetylation. Cancer Res 70(12):4931–4940CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Pützer BM, Engelmann D (2013) E2F1 apoptosis counterattacked: evil strikes back. Trends Mol Med 19(2):89–98CrossRefPubMedGoogle Scholar
  19. 19.
    Sears RC, Nevins JR (2002) Signaling networks that link cell proliferation and cell fate. J Biol Chem 277(14):11617–11620CrossRefPubMedGoogle Scholar
  20. 20.
    Zhang, E., Yin, D., Han, L., He, X., Si, X., Chen, W., ... Guo, R. (2016). E2F1-induced up regulation of long noncoding RNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs. Oncotarget 7(17):23212Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd 2017

Authors and Affiliations

  • I. Vasavi
    • 1
  • A. M. V. N. Prathyusha
    • 2
  • Malothu Ramesh
    • 3
  • K. Satish Kumar
    • 4
  • B. Pratap Naidu
    • 2
  • Pallaval Veera Bramhachari
    • 2
    Email author
  • N. M. Yugandhar
    • 5
  • P. Rama Chandra Ganesh
    • 6
  1. 1.Department of BiochemistryUniversity of LeicesterLeicesterUK
  2. 2.Department of BiotechnologyKrishna UniversityMachilipatnamIndia
  3. 3.Department of BiotechnologyJNTUKakinadaIndia
  4. 4.Department of ZoologyAdikavi Nannaya UniversityRajamundryIndia
  5. 5.Department of Chemical EngineeringAndhra UniversityVisakhapatnamIndia
  6. 6.Department of Marine Living ResourcesAndhra UniversityVisakhapatnamIndia

Personalised recommendations