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Gene Review

E2f3  -  E2F transcription factor 3

Mus musculus

Synonyms: E2F-3, E2F3b, E2f3a, Transcription factor E2F3
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Disease relevance of E2f3


High impact information on E2f3


Biological context of E2f3

  • Mutation of E2f3 dramatically impairs the mitogen-induced, transcriptional activation of numerous E2F-responsive genes [7].
  • Here we show that E2F3 also has a significant effect on the phenotype of tumor-prone Rb(+/-) mice [1].
  • We also identified patterns of gene expression that specifically differentiate the activity of E2F1 and E2F3; this profile is enriched in genes known to function in mitosis [8].
  • Gene expression profiles that distinguish either E2F1- or E2F3-expressing cells from quiescent cells are enriched in genes encoding cell cycle and DNA replication activities, consistent with many past studies [8].
  • In contrast to the E2F3a product that is tightly regulated by cell growth, the E2F3b product is expressed equivalently in quiescent and proliferating cells [9].

Anatomical context of E2f3


Associations of E2f3 with chemical compounds

  • As opposed to UVB-exposed skin, UVB-induced tumors showed elevated levels of E2F1, but these were reduced in silibinin-treated tumors without any effect on E2F2 and E2F3 [14].

Physical interactions of E2f3


Regulatory relationships of E2f3

  • E2F3 loss suppresses the development of the pituitary tumors that normally account for the death of Rb(+/-) mice [1].
  • We now show that additional E2F target genes share a common promoter architecture and are also regulated by the combined action of TFE3 and E2F3 [16].
  • In contrast, the thymidine kinase (TK-1) promoter is also regulated by E2F3 but independent of TFE3 [16].

Other interactions of E2f3

  • E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos [6].
  • Consistent with this notion, Arf mutation suppresses the activation of p53 and p21(Cip1) in E2f3-deficient MEFs [5].


  1. E2F3 loss has opposing effects on different pRB-deficient tumors, resulting in suppression of pituitary tumors but metastasis of medullary thyroid carcinomas. Ziebold, U., Lee, E.Y., Bronson, R.T., Lees, J.A. Mol. Cell. Biol. (2003) [Pubmed]
  2. Expression patterns of the E2F family of transcription factors during mouse nervous system development. Dagnino, L., Fry, C.J., Bartley, S.M., Farnham, P., Gallie, B.L., Phillips, R.A. Mech. Dev. (1997) [Pubmed]
  3. Divergent siblings: E2F2 and E2F4 but not E2F1 and E2F3 induce DNA synthesis in cardiomyocytes without activation of apoptosis. Ebelt, H., Hufnagel, N., Neuhaus, P., Neuhaus, H., Gajawada, P., Simm, A., Müller-Werdan, U., Werdan, K., Braun, T. Circ. Res. (2005) [Pubmed]
  4. Rb is critical in a mammalian tissue stem cell population. Wenzel, P.L., Wu, L., de Bruin, A., Chong, J.L., Chen, W.Y., Dureska, G., Sites, E., Pan, T., Sharma, A., Huang, K., Ridgway, R., Mosaliganti, K., Sharp, R., Machiraju, R., Saltz, J., Yamamoto, H., Cross, J.C., Robinson, M.L., Leone, G. Genes Dev. (2007) [Pubmed]
  5. Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kinetics. Aslanian, A., Iaquinta, P.J., Verona, R., Lees, J.A. Genes Dev. (2004) [Pubmed]
  6. E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Ziebold, U., Reza, T., Caron, A., Lees, J.A. Genes Dev. (2001) [Pubmed]
  7. E2f3 is critical for normal cellular proliferation. Humbert, P.O., Verona, R., Trimarchi, J.M., Rogers, C., Dandapani, S., Lees, J.A. Genes Dev. (2000) [Pubmed]
  8. Distinctions in the specificity of E2F function revealed by gene expression signatures. Black, E.P., Hallstrom, T., Dressman, H.K., West, M., Nevins, J.R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Identification of a novel E2F3 product suggests a mechanism for determining specificity of repression by Rb proteins. Leone, G., Nuckolls, F., Ishida, S., Adams, M., Sears, R., Jakoi, L., Miron, A., Nevins, J.R. Mol. Cell. Biol. (2000) [Pubmed]
  10. Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 Is Essential for G1/S Progression and Cellular Transformation. Sharma, N., Timmers, C., Trikha, P., Saavedra, H.I., Obery, A., Leone, G. J. Biol. Chem. (2006) [Pubmed]
  11. Multiple members of the E2F transcription factor family are the products of oncogenes. Xu, G., Livingston, D.M., Krek, W. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  12. The DP-1 transcription factor is required for keratinocyte growth and epidermal stratification. Chang, W.Y., Bryce, D.M., D'Souza, S.J., Dagnino, L. J. Biol. Chem. (2004) [Pubmed]
  13. Inactivation of E2F3 results in centrosome amplification. Saavedra, H.I., Maiti, B., Timmers, C., Altura, R., Tokuyama, Y., Fukasawa, K., Leone, G. Cancer Cell (2003) [Pubmed]
  14. Differential effect of silibinin on E2F transcription factors and associated biological events in chronically UVB-exposed skin versus tumors in SKH-1 hairless mice. Gu, M., Singh, R.P., Dhanalakshmi, S., Mohan, S., Agarwal, R. Mol. Cancer Ther. (2006) [Pubmed]
  15. Neural precursor cells differentiating in the absence of Rb exhibit delayed terminal mitosis and deregulated E2F 1 and 3 activity. Callaghan, D.A., Dong, L., Callaghan, S.M., Hou, Y.X., Dagnino, L., Slack, R.S. Dev. Biol. (1999) [Pubmed]
  16. Combinatorial gene control involving E2F and E Box family members. Giangrande, P.H., Zhu, W., Rempel, R.E., Laakso, N., Nevins, J.R. EMBO J. (2004) [Pubmed]
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