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Gene Review

E2F2  -  E2F transcription factor 2

Homo sapiens

Synonyms: E2F-2, Transcription factor E2F2
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Disease relevance of E2F2

  • A significant overexpression of the proliferation-promoting E2F1 and especially E2F2 points to a pivotal role in modulating the uncontrolled proliferation in ovarian cancer cells [1].
  • Consistent with previous studies, E2F-1, E2F-2, and E2F-3 bind specifically to the retinoblastoma protein [2].
  • METHODS: Whole human corneas were incubated for 2 hours in a solution of recombinant E1(-)/E3(-) adenovirus incorporating cDNA encoding E2F2 and green fluorescent protein (GFP) under control of a bidirectional promoter and subsequently maintained in ex vivo culture [3].
  • Co-expression of E2F-2 enhances the p53 anti-cancer effect in human glioma cells [4].

High impact information on E2F2

  • The flexibility in the middle of the E2F-2 peptide is essential for the tight association of E2F to the Rb pocket [5].
  • E7 was found to specifically activate E2F2 transcription in suprabasal keratinocytes through its ability to bind HDACs [6].
  • Reduction of E2F2 levels through the use of siRNA confirmed that E2F2 expression facilitated HPV replication but its loss did not affect cell proliferation [6].
  • Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation [7].
  • In T cells, a Tax-associated increase in steady-state E2F2 protein was also documented [8].

Chemical compound and disease context of E2F2


Biological context of E2F2

  • We find that a series of E2F binding sites confer negative control on the E2F3a promoter in quiescent cells, similar to the control of the E2F1 and E2F2 promoters [9].
  • Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals [10].
  • Melanocytes from skin types IV-VI that accumulate large amounts of brown black melanin (eumelanin), lose expression of the transcription factors E2F1 and E2F2, two key regulatory proteins, and withdraw from the cell cycle more rapidly than melanocytes from skin types I and II that accumulate red/yellow melanin (pheomelanin) [11].
  • They also suggest that pRb negatively regulates the transcription of two of the transcription factors whose activity it also represses, E2F-1 and E2F-2, and that it plays a role in downregulating the immediate-early gene response to serum stimulation [12].
  • A novel protein with E2F-like properties, designated E2F-2, was cloned by screening a HeLa cDNA library with a DNA probe derived from the DNA binding domain of E2F-1 (K. Helin, J. A. Lees, M. Vidal, N. Dyson, E. Harlow, and A. Fattaey, Cell 70:337-350, 1992) [13].

Anatomical context of E2F2


Associations of E2F2 with chemical compounds


Physical interactions of E2F2

  • This revealed that only 75 amino acids from within the DNA-binding domain of E2F-1 is sufficient for cell death and that this activity is also present in the DNA-binding domains of E2F-2 and E2F-3 [19].

Other interactions of E2F2


Analytical, diagnostic and therapeutic context of E2F2

  • Chromatin immunoprecipitation assays demonstrated that, in differentiating cells, E7 acts to inhibit HDAC binding to the E2F2 promoter resulting in activation of expression [6].
  • En face confocal microscopy of the corneal endothelial surface was used to image recombinant E2F2 expression [3].
  • RT-PCR of endothelial samples obtained 48 hours after transfection showed the presence of higher levels of reaction product for Ki67 (a 5.1-fold increase) and cyclin B1 (a 2.3-fold increase) in cells that overexpressed E2F2 than in control samples [15].


  1. Heterogeneous Cross-talk of E2F Family Members is Crucially Involved in Growth Modulatory Effects of Interferon-gamma and EGF. Reimer, D., Sadr, S., Wiedemair, A., Concin, N., Hofstetter, G., Marth, C., Zeimet, A.G. Cancer Biol. Ther. (2006) [Pubmed]
  2. E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry. Moberg, K., Starz, M.A., Lees, J.A. Mol. Cell. Biol. (1996) [Pubmed]
  3. Induction of replication in human corneal endothelial cells by E2F2 transcription factor cDNA transfer. McAlister, J.C., Joyce, N.C., Harris, D.L., Ali, R.R., Larkin, D.F. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  4. Co-expression of E2F-2 enhances the p53 anti-cancer effect in human glioma cells. Mitlianga, P.G., Kyritsis, A.P., Gomez-Manzano, C., Lemoine, M.G., Hu, M., Liu, T.J., Yung, W.K., Fueyo, J. Int. J. Oncol. (2001) [Pubmed]
  5. Structural basis for the recognition of the E2F transactivation domain by the retinoblastoma tumor suppressor. Lee, C., Chang, J.H., Lee, H.S., Cho, Y. Genes Dev. (2002) [Pubmed]
  6. HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs. Longworth, M.S., Wilson, R., Laimins, L.A. EMBO J. (2005) [Pubmed]
  7. Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation. Funke-Kaiser, H., Reichenberger, F., Köpke, K., Herrmann, S.M., Pfeifer, J., Orzechowski, H.D., Zidek, W., Paul, M., Brand, E. Hum. Mol. Genet. (2003) [Pubmed]
  8. Human T-cell leukemia virus type 1 Tax and cell cycle progression: role of cyclin D-cdk and p110Rb. Neuveut, C., Low, K.G., Maldarelli, F., Schmitt, I., Majone, F., Grassmann, R., Jeang, K.T. Mol. Cell. Biol. (1998) [Pubmed]
  9. Complex transcriptional regulatory mechanisms control expression of the E2F3 locus. Adams, M.R., Sears, R., Nuckolls, F., Leone, G., Nevins, J.R. Mol. Cell. Biol. (2000) [Pubmed]
  10. Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals. Sears, R., Ohtani, K., Nevins, J.R. Mol. Cell. Biol. (1997) [Pubmed]
  11. Aging in epidermal melanocytes: cell cycle genes and melanins. Haddad, M.M., Xu, W., Medrano, E.E. J. Investig. Dermatol. Symp. Proc. (1998) [Pubmed]
  12. Regulation of cellular genes in a chromosomal context by the retinoblastoma tumor suppressor protein. Buchmann, A.M., Swaminathan, S., Thimmapaya, B. Mol. Cell. Biol. (1998) [Pubmed]
  13. Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F. Ivey-Hoyle, M., Conroy, R., Huber, H.E., Goodhart, P.J., Oliff, A., Heimbrook, D.C. Mol. Cell. Biol. (1993) [Pubmed]
  14. Regulation of dihydrofolate reductase gene expression and E2F components in human diploid fibroblasts during growth and senescence. Good, L., Dimri, G.P., Campisi, J., Chen, K.Y. J. Cell. Physiol. (1996) [Pubmed]
  15. Effect of overexpressing the transcription factor E2F2 on cell cycle progression in rabbit corneal endothelial cells. Joyce, N.C., Harris, D.L., Mc Alister, J.C., Ali, R.R., Larkin, D.F. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  16. Differential expression of members of the E2F family of transcription factors in rodent testes. El-Darwish, K.S., Parvinen, M., Toppari, J. Reprod. Biol. Endocrinol. (2006) [Pubmed]
  17. Inhibition of retinoblastoma protein (Rb) phosphorylation at serine sites and an increase in Rb-E2F complex formation by silibinin in androgen-dependent human prostate carcinoma LNCaP cells: role in prostate cancer prevention. Tyagi, A., Agarwal, C., Agarwal, R. Mol. Cancer Ther. (2002) [Pubmed]
  18. A role for 14-3-3 tau in E2F1 stabilization and DNA damage-induced apoptosis. Wang, B., Liu, K., Lin, F.T., Lin, W.C. J. Biol. Chem. (2004) [Pubmed]
  19. DNA-binding independent cell death from a minimal proapoptotic region of E2F-1. Bell, L.A., O'prey, J., Ryan, K.M. Oncogene (2006) [Pubmed]
  20. E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. Müller, H., Bracken, A.P., Vernell, R., Moroni, M.C., Christians, F., Grassilli, E., Prosperini, E., Vigo, E., Oliner, J.D., Helin, K. Genes Dev. (2001) [Pubmed]
  21. Clinical Relevance of E2F Family Members in Ovarian Cancer--An Evaluation in a Training Set of 77 Patients. Reimer, D., Sadr, S., Wiedemair, A., Stadlmann, S., Concin, N., Hofstetter, G., M??ller-Holzner, E., Marth, C., Zeimet, A.G. Clin. Cancer Res. (2007) [Pubmed]
  22. E2F-1 and E2F-3 are functionally distinct in their ability to promote myeloid cell cycle progression and block granulocyte differentiation. Strom, D.K., Cleveland, J.L., Chellappan, S., Nip, J., Hiebert, S.W. Cell Growth Differ. (1998) [Pubmed]
  23. Fluorescence in situ hybridization analysis of chromosome 1p36 deletions in human MYCN amplified neuroblastoma. Komuro, H., Valentine, M.B., Rowe, S.T., Kidd, V.J., Makino, S., Brodeur, G.M., Cohn, S.L., Look, A.T. J. Pediatr. Surg. (1998) [Pubmed]
  24. Antitumor activity of an oncolytic adenovirus-delivered oncogene small interfering RNA. Zhang, Y.A., Nemunaitis, J., Samuel, S.K., Chen, P., Shen, Y., Tong, A.W. Cancer Res. (2006) [Pubmed]
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