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Gene Review

E2f1  -  E2F transcription factor 1

Rattus norvegicus

Synonyms: E2F-1, Transcription factor E2F1
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Disease relevance of E2f1

  • Transactivation of E2F-regulated genes by polyomavirus large T antigen: evidence for a two-step mechanism [1].
  • These results suggest that cyclin E, cdk2, cdk5 and E2F-1 play the roles in the G1/S transition being expressed by a common cellular mechanism(s) in the PRL-stimulated pre-T lymphoma cells [2].
  • The S-phase inhibitory activity of PSM-RB could be attenuated by the coinjection of SV40 T-antigen, adenovirus E1A, or a high level of E2F-1 expression plasmids [3].
  • We thus demonstrate two distinct cell cycle responses to low oxygen and suggest that alterations that lead to increased E2F can overcome hypoxic G1 arrest but that additional alterations, promoted by E1a expression, are necessary for neoplastic cells to proliferate despite anoxia [4].
  • Reductions in cyclin-dependent kinase (CDK)2 (82%) and CDK4 (77%) kinase activity in ER carcinomas were likely to account for the observed effects on retinoblastoma and E2F-1 [5].

High impact information on E2f1

  • We demonstrate that adenoviral vectors that contain transgenes driven by the E2F-1 promoter can mediate tumor-selective gene expression in vivo, allowing for eradication of established gliomas with significantly less normal tissue toxicity than seen with standard adenoviral vectors [6].
  • Here we show that p130 is the predominant Rb family member associated with E2F in neurons, that its major partner for repression of pro-apoptotic genes is E2F4, and that the p130-E2F4 complex recruits the chromatin modifiers HDAC1 and Suv39H1 to promote gene silencing and neuron survival [7].
  • Such derepression, rather than direct E2F-promoted gene activation, is required for death [8].
  • Role of c-fos and E2F in the induction of cyclin A transcription and vascular smooth muscle cell proliferation [9].
  • The ability of B-Myb to interact with the cdc2 promoter is dependent on an intact E2F binding site [10].

Chemical compound and disease context of E2f1

  • No apparent toxicity such as inflammation could be detected in blood vessels transfected with E2F decoy ODN with Optison and ultrasound [11].
  • These data indicate that hyperglycemia contributes to abnormal proliferation of VSMC by two mechanisms; the induction of NF-kappaB activation by Ang II, which facilitates transcription of certain growth factors, and the augmentation of E2F-1 in response to growth factors [12].
  • Hyperglycemia enhances VSMC proliferation with NF-kappaB activation by angiotensin II and E2F-1 augmentation by growth factors [12].

Biological context of E2f1

  • Hence, pocket protein binding by E1A might engage mechanisms for cell cycle reentry beyond those induced by E2F-1 [13].
  • Transforming growth factor beta1 (TGF-beta1)-induced hepatocyte apoptosis is associated with activation of E2F transcription factors and p53 stabilization through Mdm-2, thus potentially modulating a number of target genes [14].
  • The viral protein causes a dissociation of E2F-pocket protein complexes that results in transactivation of the genes [1].
  • The decrease in RB expression and phosphorylation, which is essential in triggering DNA synthesis and Cyclin A expression, leads to a deficiency in transcriptionally active E2F complex formation after hepatectomy [15].
  • RESULTS: E2F1 increased 20-fold in G1/S phase transition [16].

Anatomical context of E2f1

  • E1A can evoke G1 exit in cardiac myocytes and other cell types by displacing E2F transcription factors from tumor suppressor "pocket" proteins and by a less well-characterized p300-dependent pathway [13].
  • Thus, E2F-1-induced Cdk2 function was necessary, although not sufficient, to trigger DNA synthesis in cardiac muscle cells [13].
  • E2F1 regulates the mesangial cell cycle through two distinct pathways [16].
  • Differences in E2F subunit expression in quiescent and proliferating vascular smooth muscle cells [17].
  • Indeed, overexpression of E2F proteins, including the E2F1 and E2F2 products, induces DNA synthesis in quiescent fibroblasts [18].

Associations of E2f1 with chemical compounds


Physical interactions of E2f1

  • Analysis of the transcription factor E2F complexes formed in the promoter regions of cdc2 and dihydrofolate reductase genes showed that the amount of complexes formed is maximal at the G1/S boundary, but decreases in S phase when these genes are transcribed extensively [22].

Regulatory relationships of E2f1

  • Although this could represent a response to aberrant cell cycle progression, we show that only E2F1 induces apoptosis and that this coincides with an ability of E2F1 to induce accumulation of p53 protein [18].
  • These experiments revealed that deregulated E2F-1 expression triggers high levels of cyclin E and A expression and kinase activities in small early G1 cells, normally not exhibiting these activities [23].
  • Deregulated expression of E2F-1 induces cyclin A- and E-associated kinase activities independently from cell cycle position [23].

Other interactions of E2f1

  • RESULTS: The activity of Cdk2, the protein amount of pRB, Ser795 phosphorylation of pRB, and the protein amount of E2F1 were all increased compared with the sham-treated control subjects, and these increases were enhanced with the increasing number of ECS [24].
  • FBS induced upregulation of E2F-1 and E2F-5 at both mRNA and protein levels and slightly reduced E2F-3 protein [17].
  • In nodules and/or HCCs of Wistar and BN rats, low or no increases in c-myc, Cyclins D1, E, and A, and E2F1 expression, and Cyclin-CDKs complex formation were associated with p16(INK4A) overexpression and pRb hypophosphorylation [25].
  • As determined by appropriate combinations of immunoprecipitations, Western blots, and kinase activity assays, it was found that levels of phosphorylated retinoblastoma and E2F-1 were significantly reduced by ER (approximately 40 and 75%, respectively; P < 0.01), an effect that was partially reversed by ER-REP [5].
  • In conclusion, the results demonstrate that Abeta-induced apoptosis of PC12 cells proceeds through an E2F-1/p53/Bax pathway, which, in turn, can be specifically inhibited by TUDCA, thus underscoring its potential therapeutic use [20].

Analytical, diagnostic and therapeutic context of E2f1


  1. Transactivation of E2F-regulated genes by polyomavirus large T antigen: evidence for a two-step mechanism. Nemethova, M., Smutny, M., Wintersberger, E. Mol. Cell. Biol. (2004) [Pubmed]
  2. Synergistic gene expressions of cyclin E, cdk2, cdk5 and E2F-1 during the prolactin-induced G1/S transition in rat Nb2 pre-T lymphoma cells. Hosokawa, Y., Yang, M., Kaneko, S., Tanaka, M., Nakashima, K. Biochem. Mol. Biol. Int. (1995) [Pubmed]
  3. Inhibition of DNA synthesis by RB: effects on G1/S transition and S-phase progression. Knudsen, E.S., Buckmaster, C., Chen, T.T., Feramisco, J.R., Wang, J.Y. Genes Dev. (1998) [Pubmed]
  4. Anoxic fibroblasts activate a replication checkpoint that is bypassed by E1a. Gardner, L.B., Li, F., Yang, X., Dang, C.V. Mol. Cell. Biol. (2003) [Pubmed]
  5. Effect of energy restriction on cell cycle machinery in 1-methyl-1-nitrosourea-induced mammary carcinomas in rats. Jiang, W., Zhu, Z., Thompson, H.J. Cancer Res. (2003) [Pubmed]
  6. Tumor-selective transgene expression in vivo mediated by an E2F-responsive adenoviral vector. Parr, M.J., Manome, Y., Tanaka, T., Wen, P., Kufe, D.W., Kaelin, W.G., Fine, H.A. Nat. Med. (1997) [Pubmed]
  7. Regulation of neuron survival and death by p130 and associated chromatin modifiers. Liu, D.X., Nath, N., Chellappan, S.P., Greene, L.A. Genes Dev. (2005) [Pubmed]
  8. Regulation of neuronal survival and death by E2F-dependent gene repression and derepression. Liu, D.X., Greene, L.A. Neuron (2001) [Pubmed]
  9. Role of c-fos and E2F in the induction of cyclin A transcription and vascular smooth muscle cell proliferation. Sylvester, A.M., Chen, D., Krasinski, K., Andrés, V. J. Clin. Invest. (1998) [Pubmed]
  10. E2Fs link the control of G1/S and G2/M transcription. Zhu, W., Giangrande, P.H., Nevins, J.R. EMBO J. (2004) [Pubmed]
  11. Local delivery of E2F decoy oligodeoxynucleotides using ultrasound with microbubble agent (Optison) inhibits intimal hyperplasia after balloon injury in rat carotid artery model. Hashiya, N., Aoki, M., Tachibana, K., Taniyama, Y., Yamasaki, K., Hiraoka, K., Makino, H., Yasufumi, K., Ogihara, T., Morishita, R. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  12. Hyperglycemia enhances VSMC proliferation with NF-kappaB activation by angiotensin II and E2F-1 augmentation by growth factors. Fujita, N., Furukawa, Y., Du, J., Itabashi, N., Fujisawa, G., Okada, K., Saito, T., Ishibashi, S. Mol. Cell. Endocrinol. (2002) [Pubmed]
  13. E1A can provoke G1 exit that is refractory to p21 and independent of activating cdk2. Akli, S., Zhan, S., Abdellatif, M., Schneider, M.D. Circ. Res. (1999) [Pubmed]
  14. Ursodeoxycholic acid modulates E2F-1 and p53 expression through a caspase-independent mechanism in transforming growth factor beta1-induced apoptosis of rat hepatocytes. Sola, S., Ma, X., Castro, R.E., Kren, B.T., Steer, C.J., Rodrigues, C.M. J. Biol. Chem. (2003) [Pubmed]
  15. 2-acetaminofluorene blocks cell cycle progression after hepatectomy by p21 induction and lack of cyclin E expression. Trautwein, C., Will, M., Kubicka, S., Rakemann, T., Flemming, P., Manns, M.P. Oncogene (1999) [Pubmed]
  16. Roles of E2F1 in mesangial cell proliferation in vitro. Inoshita, S., Terada, Y., Nakashima, O., Kuwahara, M., Sasaki, S., Marumo, F. Kidney Int. (1999) [Pubmed]
  17. Differences in E2F subunit expression in quiescent and proliferating vascular smooth muscle cells. Fujita, N., Furukawa, Y., Itabashi, N., Okada, K., Saito, T., Ishibashi, S. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  18. E2F1-specific induction of apoptosis and p53 accumulation, which is blocked by Mdm2. Kowalik, T.F., DeGregori, J., Leone, G., Jakoi, L., Nevins, J.R. Cell Growth Differ. (1998) [Pubmed]
  19. Mitoinhibitory effects of the tumor promoter 2-acetylaminofluorene in rat liver: loss of E2F-1 and E2F-3 expression and cdk 2 kinase activity in late G1. Ohlson, L.C., Koroxenidou, L., Porsch-Hällström, I. J. Hepatol. (2004) [Pubmed]
  20. Inhibition of the E2F-1/p53/Bax pathway by tauroursodeoxycholic acid in amyloid beta-peptide-induced apoptosis of PC12 cells. Ramalho, R.M., Ribeiro, P.S., Solá, S., Castro, R.E., Steer, C.J., Rodrigues, C.M. J. Neurochem. (2004) [Pubmed]
  21. Modulation of nuclear steroid receptors by ursodeoxycholic acid inhibits TGF-beta1-induced E2F-1/p53-mediated apoptosis of rat hepatocytes. Solá, S., Castro, R.E., Kren, B.T., Steer, C.J., Rodrigues, C.M. Biochemistry (2004) [Pubmed]
  22. Differential activation of cyclin and cyclin-dependent kinase genes by adenovirus E1A12S cDNA product. Ishii, T., Shimizu, M., Kanayama, Y., Nakada, S., Nojima, H., Oda, K. Exp. Cell Res. (1993) [Pubmed]
  23. Deregulated expression of E2F-1 induces cyclin A- and E-associated kinase activities independently from cell cycle position. Soucek, T., Pusch, O., Hengstschläger-Ottnad, E., Adams, P.D., Hengstschläger, M. Oncogene (1997) [Pubmed]
  24. Activation of Cdk2-pRB-E2F1 cell cycle pathway by repeated electroconvulsive shock in the rat frontal cortex. Kim, Y., Seo, M.S., Kang, U.G., Yoon, S.C., Ahn, Y.M., Kim, Y.S., Juhnn, Y.S. Biol. Psychiatry (2005) [Pubmed]
  25. Cell cycle deregulation in liver lesions of rats with and without genetic predisposition to hepatocarcinogenesis. Pascale, R.M., Simile, M.M., De Miglio, M.R., Muroni, M.R., Calvisi, D.F., Asara, G., Casabona, D., Frau, M., Seddaiu, M.A., Feo, F. Hepatology (2002) [Pubmed]
  26. pRb and p107 regulate E2F activity during lens fiber cell differentiation. Rampalli, A.M., Gao, C.Y., Chauthaiwale, V.M., Zelenka, P.S. Oncogene (1998) [Pubmed]
  27. A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle proliferation in vivo. Morishita, R., Gibbons, G.H., Horiuchi, M., Ellison, K.E., Nakama, M., Zhang, L., Kaneda, Y., Ogihara, T., Dzau, V.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
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