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Gene Review

E2F3  -  E2F transcription factor 3

Homo sapiens

Synonyms: E2F-3, KIAA0075, Transcription factor E2F3
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Disease relevance of E2F3

  • When patients are stratified according to the maximum percentage of E2F3-positive nuclei identified within their prostate cancers (up to 20, 21-40%, etc.), there is an increasingly significant association between E2F3 staining and risk of death both for overall survival (P=0.0014) and for cause-specific survival (P=0.0004) [1].
  • In summary, our results suggest that DEK and E2F3 are potential targets of 6p gains in retinoblastoma [2].
  • Nuclear overexpression of the E2F3 transcription factor in human lung cancer [3].
  • RESULTS: E2F3 is overexpressed in 55-70% of squamous cell carcinomas and 79% of adenocarcinomas of the lung [3].
  • METHODS: Immunohistochemical techniques were used to assess the E2F3 status in 428 samples of lung cancers, lung carcinoids, normal bronchial epithelium and normal lung tissue [3].

High impact information on E2F3

  • Moreover, whereas overall E2F DNA-binding activity accumulates during the initial G1 following a growth stimulus, only E2F3-binding activity reaccumulates at subsequent G1/S transitions, coincident with the expression of the cell-cycle-regulated subset of E2F-target genes [4].
  • We propose that E2F3 activity plays an important role during the cell cycle of proliferating cells, controlling the expression of genes whose products are rate limiting for initiation of DNA replication, thereby imparting a more dramatic control of entry into S phase than would otherwise be achieved by post-transcriptional control alone [4].
  • Finally, we show that immunodepletion of E2F3 activity inhibits the induction of S phase in proliferating cells [4].
  • However, the E2F-2 and E2F-3 proteins are closely related to E2F-1 [5].
  • Both E2F-2 and E2F-3 bound to wild-type but not mutant E2F recognition sites, and they bound specifically to the retinoblastoma protein in vivo [5].

Biological context of E2F3

  • We have shown that the E2F3 locus encodes two protein products: the E2F3a product, which is tightly regulated by cell growth, and the E2F3b product, which is constitutively expressed throughout the cell cycle [6].
  • Previous work has shown that the expression of the E2F1, E2F2, and E2F3 gene products is tightly regulated by cell growth [7].
  • We propose a model whereby miR-17-92 promotes cell proliferation by shifting the E2F transcriptional balance away from the pro-apoptotic E2F1 and toward the proliferative E2F3 transcriptional network [8].
  • Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma [2].
  • Depletion of 14-3-3 tau or E2F1, but not E2F2 or E2F3, blocks adriamycin-induced apoptosis [9].

Anatomical context of E2F3


Associations of E2F3 with chemical compounds

  • In other studies, silibinin showed a moderate effect on E2F1 but up to 98 and 90% decreases in E2F2 and E2F3 protein levels, respectively [14].

Regulatory relationships of E2F3

  • We also find that the acute loss of E2F3 activity affects the expression of genes encoding DNA replication and mitotic activities, whereas loss of E2F1 affects a limited number of genes that are distinct from those regulated by E2F3 [15].
  • Moreover, we observed that BRD7 could regulate the promoter activity of E2F3, one of its targets [16].

Other interactions of E2F3

  • Surprisingly, E2F-1 and E2F-3 make unequal contributions to the pRB-associated and free E2F activity, suggesting that these proteins perform different cell cycle functions [17].
  • In addition, there was a significant complementary association between gain of CCND1 and gain of E2F3 [18].
  • Activation of BS2 and BS3 are E2F1-specific, since neither E2F2 nor E2F3 is able to activate BS2 or BS3 [19].
  • When these results are considered together with published data on EZH2 and on the E2F3 control protein pRB, we conclude that the pRB-E2F3-EZH2 control axis may have a critical role in modulating aggressiveness of individual human prostate cancer [1].
  • Moreover, an increase in DP-1 and E2F3 is probably involved in the proliferation-enhancing effect of EGF [20].

Analytical, diagnostic and therapeutic context of E2F3


  1. Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome. Foster, C.S., Falconer, A., Dodson, A.R., Norman, A.R., Dennis, N., Fletcher, A., Southgate, C., Dowe, A., Dearnaley, D., Jhavar, S., Eeles, R., Feber, A., Cooper, C.S. Oncogene (2004) [Pubmed]
  2. Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma. Grasemann, C., Gratias, S., Stephan, H., Schüler, A., Schramm, A., Klein-Hitpass, L., Rieder, H., Schneider, S., Kappes, F., Eggert, A., Lohmann, D.R. Oncogene (2005) [Pubmed]
  3. Nuclear overexpression of the E2F3 transcription factor in human lung cancer. Cooper, C.S., Nicholson, A.G., Foster, C., Dodson, A., Edwards, S., Fletcher, A., Roe, T., Clark, J., Joshi, A., Norman, A., Feber, A., Lin, D., Gao, Y., Shipley, J., Cheng, S.J. Lung Cancer (2006) [Pubmed]
  4. E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Leone, G., DeGregori, J., Yan, Z., Jakoi, L., Ishida, S., Williams, R.S., Nevins, J.R. Genes Dev. (1998) [Pubmed]
  5. The retinoblastoma protein binds to a family of E2F transcription factors. Lees, J.A., Saito, M., Vidal, M., Valentine, M., Look, T., Harlow, E., Dyson, N., Helin, K. Mol. Cell. Biol. (1993) [Pubmed]
  6. 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]
  7. 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]
  8. Direct Regulation of an Oncogenic Micro-RNA Cluster by E2F Transcription Factors. Woods, K., Thomson, J.M., Hammond, S.M. J. Biol. Chem. (2007) [Pubmed]
  9. 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]
  10. Regulation of the G1/S transition phase in mesangial cells by E2F1. Inoshita, S., Terada, Y., Nakashima, O., Kuwahara, M., Sasaki, S., Marumo, F. Kidney Int. (1999) [Pubmed]
  11. Differentiation and injury-repair signals modulate the interaction of E2F and pRB proteins with novel target genes in keratinocytes. Chang, W.Y., Andrews, J., Carter, D.E., Dagnino, L. Cell Cycle (2006) [Pubmed]
  12. E2F3 is the main target gene of the 6p22 amplicon with high specificity for human bladder cancer. Oeggerli, M., Schraml, P., Ruiz, C., Bloch, M., Novotny, H., Mirlacher, M., Sauter, G., Simon, R. Oncogene (2006) [Pubmed]
  13. 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]
  14. 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]
  15. Compensation and specificity of function within the E2F family. Kong, L.J., Chang, J.T., Bild, A.H., Nevins, J.R. Oncogene (2007) [Pubmed]
  16. BRD7, a novel bromodomain gene, inhibits G1-S progression by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathways. Zhou, J., Ma, J., Zhang, B.C., Li, X.L., Shen, S.R., Zhu, S.G., Xiong, W., Liu, H.Y., Huang, H., Zhou, M., Li, G.Y. J. Cell. Physiol. (2004) [Pubmed]
  17. 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]
  18. Array-based comparative genomic hybridization for genome-wide screening of DNA copy number in bladder tumors. Veltman, J.A., Fridlyand, J., Pejavar, S., Olshen, A.B., Korkola, J.E., DeVries, S., Carroll, P., Kuo, W.L., Pinkel, D., Albertson, D., Cordon-Cardo, C., Jain, A.N., Waldman, F.M. Cancer Res. (2003) [Pubmed]
  19. Novel link between E2F1 and Smac/DIABLO: proapoptotic Smac/DIABLO is transcriptionally upregulated by E2F1. Xie, W., Jiang, P., Miao, L., Zhao, Y., Zhimin, Z., Qing, L., Zhu, W.G., Wu, M. Nucleic Acids Res. (2006) [Pubmed]
  20. 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]
  21. E2F3 amplification and overexpression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer. Oeggerli, M., Tomovska, S., Schraml, P., Calvano-Forte, D., Schafroth, S., Simon, R., Gasser, T., Mihatsch, M.J., Sauter, G. Oncogene (2004) [Pubmed]
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