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Gene Review

E2F1  -  E2F transcription factor 1

Homo sapiens

Synonyms: E2F-1, PBR3, RBAP-1, RBAP1, RBBP-3, ...
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Disease relevance of E2F1

  • E2F1 was the only family member more abundant in the melanoma cells compared with normal melanocytes, and the approximately fivefold increase in DNA binding activity could be accounted for mostly by a similar increase in the levels of the dimerization partner DP1 [1].
  • Most important, the endogenous cyclin E gene is activated following expression of the E2F1 product encoded by a recombinant adenovirus vector [2].
  • ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance [3].
  • We show that E2F1 expression is low in benign and localized prostate cancer, modestly elevated in metastatic lymph nodes from hormone-na??ve patients, and significantly elevated in metastatic tissues from hormone-resistant prostate cancer patients (P = 0.0006) [4].
  • Thus, deregulation of the E2F1-responsive P1 promoter, rather than the alternate P2 promoter, is mainly responsible for the production of transdominant p53/TAp73 antagonists in ovarian cancer [5].
  • E2F-1 is a potentially novel independent prognostic factor that may identify gastric cancer patients who will likely benefit from adjuvant chemoradiation therapy following curative resection [6].

Psychiatry related information on E2F1


High impact information on E2F1


Chemical compound and disease context of E2F1


Biological context of E2F1


Anatomical context of E2F1

  • We have also used a recombinant adenovirus containing the human E2F1 gene to overexpress the E2F1 product in mink lung epithelial cells that were growth arrested with TGF-beta [23].
  • These data are consistent with the notion that E2F1 is a regulator of chondrocyte differentiation [24].
  • Here, we demonstrate that C/EBPepsilon interacts with Rb and E2F1 during granulocytic differentiation in NB4 and U937 human myeloid cells and in 32Dcl3 murine myeloid precursor cells [25].
  • We found a large number of binding sites for all three factors; extrapolation suggests there may be approximately 20,000-30,000 E2F1- and MYC-binding sites and approximately 12,000-17,000 active promoters in HeLa cells [26].
  • Localization studies showed that DIP localizes to the mitochondria, where endogenous DIP is upregulated following E2F1 induction [27].

Associations of E2F1 with chemical compounds

  • The acetylation sites lie adjacent to the E2F1 DNA-binding domain and involve lysine residues highly conserved in E2F1, 2 and 3 [28].
  • Several other candidates, including the dihydrofolate reductase and thymidine kinase genes, were only minimally induced by E2F1 [29].
  • We found that acetylation of E2F1 is, instead, required to stabilize the protein in response to doxorubicin [30].
  • First, an estrogen receptor-E2F1 fusion protein (ER-E2F1) potently activates the endogenous cyclin D3 mRNA upon treatment with 4-hydroxytamoxifen, which induces nuclear accumulation of the otherwise cytosolic fusion protein [31].
  • A dominant negative mutant (E2F97) of E2F1 containing the DNA binding domain of E2F1 under the control of a tetracycline-responsive promoter was constructed [32].

Physical interactions of E2F1

  • TRRAP also interacts specifically with the E2F-1 transactivation domain [33].
  • All the cyclin A binding E2F family members can interact and cooperate with p53 to induce apoptosis [34].
  • E2F-5 resembles the other E2Fs in that it binds to a consensus E2F site in a cooperative fashion with DP-1 [35].
  • E2F6 contains a DNA binding domain that is very similar to that of the other members of the E2F family of transcriptional regulators [36].
  • Free E2F4 was found to be the predominant species bound to the E2F sites in proliferating cells [37].
  • Together with the observation that E2F1 physically interacts with p50/RELA in LPS-stimulated cells, our findings suggest that NF-kappaB recruits E2F1 to fully activate the transcription of NF-kappaB target genes [38].

Enzymatic interactions of E2F1

  • However, these cyclin/kinase complexes exhibit differences in the ability to phosphorylate E2F [39].
  • Only cyclin A/cdk2 can phosphorylate E2F effectively, and this phosphorylation abolishes its ability to bind DNA and mediate trans-activation [39].
  • Therefore, Chk2 phosphorylates and activates E2F-1 in response to DNA damage, resulting in apoptosis [40].
  • Formation of this complex was not inducible by IFN alpha in U937VR cells, although the suitable binding partners (E2F-1 and under-phosphorylated RB) were present [41].

Regulatory relationships of E2F1

  • Elevation of ACTR in quiescent cells strongly stimulates the transcription of a subset of E2F-responsive genes that are associated with the G(1)/S transition [3].
  • In addition, E2F1 can induce apoptosis via both p53-dependent and p53-independent pathways [42].
  • Prohibitin thus appears to repress E2F-mediated transcription utilizing different molecular mediators and facilitate channeling of specific signaling pathways to the cell cycle machinery [43].
  • Finally, expression of p21 specifically inhibited transcription from an E2F-dependent promoter but had no effect on a mutant E2 promoter [44].
  • Expression of HDAC1 with Sp1 suppressed promoter activity and suppression was not alleviated by coexpression of E2F1/DP1 [45].
  • Endogenous E2F-1 upregulates PAC1 and suppresses ERK activity, leading to cell death in response to 4-HPR [46].
  • Ectopic expression of KAP1 represses E2F1 transcription and apoptosis functions independent of pRb [47].
  • We first evidenced the complex interaction between RIP140 and E2F1 and showed that RIP140 represses E2F1 transactivation on various transiently transfected E2F target promoters and inhibits the expression of several E2F1 target genes (such as CCNE1 and CCNB2) [48].

Other interactions of E2F1

  • These data suggest that TRRAP is an essential cofactor for both the c-Myc and E1A/E2F oncogenic transcription factor pathways [33].
  • A new component of the transcription factor DRTF1/E2F [49].
  • We have used high-density oligonucleotide arrays to identify genes in which expression changed in response to activation of E2F1, E2F2, and E2F3 [50].
  • By gel shift analysis, we show that in mitogen-dependent normal melanocytes, external growth factors tightly controlled the levels of growth-promoting free E2F DNA binding activity, composed largely of E2F2 and E2F4, and the growth-suppressive E2F4-p130 complexes [1].
  • E2F-dependent regulation of the CCNE1 promoter was shown to correlate with changes in the level of H3-K9 acetylation/methylation of nucleosomal histones positioned at the transcriptional start site region [51].

Analytical, diagnostic and therapeutic context of E2F1


  1. Deregulated E2F transcriptional activity in autonomously growing melanoma cells. Halaban, R., Cheng, E., Smicun, Y., Germino, J. J. Exp. Med. (2000) [Pubmed]
  2. Regulation of the cyclin E gene by transcription factor E2F1. Ohtani, K., DeGregori, J., Nevins, J.R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance. Louie, M.C., Zou, J.X., Rabinovich, A., Chen, H.W. Mol. Cell. Biol. (2004) [Pubmed]
  4. Elevated E2F1 inhibits transcription of the androgen receptor in metastatic hormone-resistant prostate cancer. Davis, J.N., Wojno, K.J., Daignault, S., Hofer, M.D., Kuefer, R., Rubin, M.A., Day, M.L. Cancer Res. (2006) [Pubmed]
  5. Transdominant DeltaTAp73 isoforms are frequently up-regulated in ovarian cancer. Evidence for their role as epigenetic p53 inhibitors in vivo. Concin, N., Becker, K., Slade, N., Erster, S., Mueller-Holzner, E., Ulmer, H., Daxenbichler, G., Zeimet, A., Zeillinger, R., Marth, C., Moll, U.M. Cancer Res. (2004) [Pubmed]
  6. Impact of E2F-1 expression on clinical outcome of gastric adenocarcinoma patients with adjuvant chemoradiation therapy. Lee, J., Park, C.K., Park, J.O., Lim, T., Park, Y.S., Lim, H.Y., Lee, I., Sohn, T.S., Noh, J.H., Heo, J.S., Kim, S., Lim, D.H., Kim, K.M., Kang, W.K. Clin. Cancer Res. (2008) [Pubmed]
  7. Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology. Shimizu, S., Khan, M.Z., Hippensteel, R.L., Parkar, A., Raghupathi, R., Meucci, O. Neurobiol. Dis. (2007) [Pubmed]
  8. Gene therapy approaches for the selective killing of cancer cells. Westphal, E.M., Melchner Hv, H. Curr. Pharm. Des. (2002) [Pubmed]
  9. Up-regulation of E2F-1 in Down's syndrome brain exhibiting neuropathological features of Alzheimer-type dementia. Motonaga, K., Itoh, M., Hirayama, A., Hirano, S., Becker, L.E., Goto, Y., Takashima, S. Brain Res. (2001) [Pubmed]
  10. Re-Evaluating Cell-Cycle Regulation by E2Fs. Rowland, B.D., Bernards, R. Cell (2006) [Pubmed]
  11. Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release. Rubin, S.M., Gall, A.L., Zheng, N., Pavletich, N.P. Cell (2005) [Pubmed]
  12. A variable number of tandem repeats polymorphism in an E2F-1 binding element in the 5' flanking region of SMYD3 is a risk factor for human cancers. Tsuge, M., Hamamoto, R., Silva, F.P., Ohnishi, Y., Chayama, K., Kamatani, N., Furukawa, Y., Nakamura, Y. Nat. Genet. (2005) [Pubmed]
  13. E2F1 expression in LNCaP prostate cancer cells deregulates androgen dependent growth, suppresses differentiation, and enhances apoptosis. Libertini, S.J., Tepper, C.G., Guadalupe, M., Lu, Y., Asmuth, D.M., Mudryj, M. Prostate (2006) [Pubmed]
  14. All-trans retinoic acid converts E2F into a transcriptional suppressor and inhibits the growth of normal human bronchial epithelial cells through a retinoic acid receptor- dependent signaling pathway. Lee, H.Y., Dohi, D.F., Kim, Y.H., Walsh, G.L., Consoli, U., Andreeff, M., Dawson, M.I., Hong, W.K., Kurie, J.M. J. Clin. Invest. (1998) [Pubmed]
  15. Tumor necrosis factor alpha inhibits cyclin A expression and retinoblastoma hyperphosphorylation triggered by insulin-like growth factor-I induction of new E2F-1 synthesis. Shen, W.H., Yin, Y., Broussard, S.R., McCusker, R.H., Freund, G.G., Dantzer, R., Kelley, K.W. J. Biol. Chem. (2004) [Pubmed]
  16. 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]
  17. In human salivary gland cells, overexpression of E2F1 overcomes an interferon-gamma- and tumor necrosis factor-alpha-induced growth arrest but does not result in complete mitosis. Lillibridge, C.D., O'Connell, B.C. J. Cell. Physiol. (1997) [Pubmed]
  18. Role of the p53-homologue p73 in E2F1-induced apoptosis. Stiewe, T., Pützer, B.M. Nat. Genet. (2000) [Pubmed]
  19. Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Magnaghi-Jaulin, L., Groisman, R., Naguibneva, I., Robin, P., Lorain, S., Le Villain, J.P., Troalen, F., Trouche, D., Harel-Bellan, A. Nature (1998) [Pubmed]
  20. Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. Johnson, D.G., Ohtani, K., Nevins, J.R. Genes Dev. (1994) [Pubmed]
  21. Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Lin, W.C., Lin, F.T., Nevins, J.R. Genes Dev. (2001) [Pubmed]
  22. TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival. Liu, K., Luo, Y., Lin, F.T., Lin, W.C. Genes Dev. (2004) [Pubmed]
  23. Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression. Schwarz, J.K., Bassing, C.H., Kovesdi, I., Datto, M.B., Blazing, M., George, S., Wang, X.F., Nevins, J.R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  24. Constitutive E2F1 overexpression delays endochondral bone formation by inhibiting chondrocyte differentiation. Scheijen, B., Bronk, M., van der Meer, T., Bernards, R. Mol. Cell. Biol. (2003) [Pubmed]
  25. C/EBPepsilon interacts with retinoblastoma and E2F1 during granulopoiesis. Gery, S., Gombart, A.F., Fung, Y.K., Koeffler, H.P. Blood (2004) [Pubmed]
  26. Unbiased location analysis of E2F1-binding sites suggests a widespread role for E2F1 in the human genome. Bieda, M., Xu, X., Singer, M.A., Green, R., Farnham, P.J. Genome Res. (2006) [Pubmed]
  27. A novel mitochondrial protein DIP mediates E2F1-induced apoptosis independently of p53. Stanelle, J., Tu-Rapp, H., Pützer, B.M. Cell Death Differ. (2005) [Pubmed]
  28. Regulation of E2F1 activity by acetylation. Martínez-Balbás, M.A., Bauer, U.M., Nielsen, S.J., Brehm, A., Kouzarides, T. EMBO J. (2000) [Pubmed]
  29. Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes. DeGregori, J., Kowalik, T., Nevins, J.R. Mol. Cell. Biol. (1995) [Pubmed]
  30. Specific role for p300/CREB-binding protein-associated factor activity in E2F1 stabilization in response to DNA damage. Ianari, A., Gallo, R., Palma, M., Alesse, E., Gulino, A. J. Biol. Chem. (2004) [Pubmed]
  31. Regulation of the cyclin D3 promoter by E2F1. Ma, Y., Yuan, J., Huang, M., Jove, R., Cress, W.D. J. Biol. Chem. (2003) [Pubmed]
  32. Functional roles of E2F in cell cycle regulation. Fan, J., Bertino, J.R. Oncogene (1997) [Pubmed]
  33. The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. McMahon, S.B., Van Buskirk, H.A., Dugan, K.A., Copeland, T.D., Cole, M.D. Cell (1998) [Pubmed]
  34. Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage. Hsieh, J.K., Yap, D., O'Connor, D.J., Fogal, V., Fallis, L., Chan, F., Zhong, S., Lu, X. Mol. Cell. Biol. (2002) [Pubmed]
  35. E2F-5, a new E2F family member that interacts with p130 in vivo. Hijmans, E.M., Voorhoeve, P.M., Beijersbergen, R.L., van 't Veer, L.J., Bernards, R. Mol. Cell. Biol. (1995) [Pubmed]
  36. E2F6 negatively regulates BRCA1 in human cancer cells without methylation of histone H3 on lysine 9. Oberley, M.J., Inman, D.R., Farnham, P.J. J. Biol. Chem. (2003) [Pubmed]
  37. Transcriptional repression of the E2F-1 gene by interferon-alpha is mediated through induction of E2F-4/pRB and E2F-4/p130 complexes. Furukawa, Y., Iwase, S., Kikuchi, J., Nakamura, M., Yamada, H., Matsuda, M. Oncogene (1999) [Pubmed]
  38. Genome-wide mapping of RELA(p65) binding identifies E2F1 as a transcriptional activator recruited by NF-kappaB upon TLR4 activation. Lim, C.A., Yao, F., Wong, J.J., George, J., Xu, H., Chiu, K.P., Sung, W.K., Lipovich, L., Vega, V.B., Chen, J., Shahab, A., Zhao, X.D., Hibberd, M., Wei, C.L., Lim, B., Ng, H.H., Ruan, Y., Chin, K.C. Mol. Cell (2007) [Pubmed]
  39. Differential regulation of E2F transactivation by cyclin/cdk2 complexes. Dynlacht, B.D., Flores, O., Lees, J.A., Harlow, E. Genes Dev. (1994) [Pubmed]
  40. Chk2 activates E2F-1 in response to DNA damage. Stevens, C., Smith, L., La Thangue, N.B. Nat. Cell Biol. (2003) [Pubmed]
  41. Formation of the early-region-2 transcription-factor-1-retinoblastoma-protein (E2F-1-RB) transrepressor and release of the retinoblastoma protein from nuclear complexes containing cyclin A is induced by interferon alpha in U937V cells but not in interferon-alpha-resistant U937VR cells. Kirch, H.C., Putzer, B., Brockmann, D., Esche, H., Kloke, O. Eur. J. Biochem. (1997) [Pubmed]
  42. Novel link between E2F and p53: proapoptotic cofactors of p53 are transcriptionally upregulated by E2F. Hershko, T., Chaussepied, M., Oren, M., Ginsberg, D. Cell Death Differ. (2005) [Pubmed]
  43. Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression. Wang, S., Fusaro, G., Padmanabhan, J., Chellappan, S.P. Oncogene (2002) [Pubmed]
  44. A role for a p21-E2F interaction during senescence arrest of normal human fibroblasts. Afshari, C.A., Nichols, M.A., Xiong, Y., Mudryj, M. Cell Growth Differ. (1996) [Pubmed]
  45. Modulation of Sp1-dependent transcription by a cis-acting E2F element in dhfr promoter. Park, K.K., Rue, S.W., Lee, I.S., Kim, H.C., Lee, I.K., Ahn, J.D., Kim, H.S., Yu, T.S., Kwak, J.Y., Heintz, N.H., Magae, J., Chang, Y.C. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  46. PAC1 is a direct transcription target of E2F-1 in apoptotic signaling. Wu, J., Jin, Y.J., Calaf, G.M., Huang, W.L., Yin, Y. Oncogene (2007) [Pubmed]
  47. Regulation of E2F1 function by the nuclear corepressor KAP1. Wang, C., Rauscher, F.J., Cress, W.D., Chen, J. J. Biol. Chem. (2007) [Pubmed]
  48. The transcriptional coregulator RIP140 represses E2F1 activity and discriminates breast cancer subtypes. Docquier, A., Harmand, P.O., Fritsch, S., Chanrion, M., Darbon, J.M., Cavaillès, V. Clin. Cancer Res. (2010) [Pubmed]
  49. A new component of the transcription factor DRTF1/E2F. Girling, R., Partridge, J.F., Bandara, L.R., Burden, N., Totty, N.F., Hsuan, J.J., La Thangue, N.B. Nature (1993) [Pubmed]
  50. 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]
  51. Coactivator-associated arginine methyltransferase 1 (CARM1) is a positive regulator of the Cyclin E1 gene. El Messaoudi, S., Fabbrizio, E., Rodriguez, C., Chuchana, P., Fauquier, L., Cheng, D., Theillet, C., Vandel, L., Bedford, M.T., Sardet, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  52. Differential regulation of E2F1 apoptotic target genes in response to DNA damage. Pediconi, N., Ianari, A., Costanzo, A., Belloni, L., Gallo, R., Cimino, L., Porcellini, A., Screpanti, I., Balsano, C., Alesse, E., Gulino, A., Levrero, M. Nat. Cell Biol. (2003) [Pubmed]
  53. Disruption of the pRb/E2F pathway and inhibition of apoptosis are major oncogenic events in liver constitutively expressing c-myc and transforming growth factor alpha. Santoni-Rugiu, E., Jensen, M.R., Thorgeirsson, S.S. Cancer Res. (1998) [Pubmed]
  54. Opposite functions for E2F1 and E2F4 in human epidermal keratinocyte differentiation. Paramio, J.M., Segrelles, C., Casanova, M.L., Jorcano, J.L. J. Biol. Chem. (2000) [Pubmed]
  55. Modulation of E2F activity via signaling through surface IgM and CD40 receptors in WEHI-231 B lymphoma cells. Lam, E.W., Choi, M.S., van der Sman, J., Burbidge, S.A., Klaus, G.G. J. Biol. Chem. (1998) [Pubmed]
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