Gene Symbol: E2f1
Description: E2F transcription factor 1
Alias: E2F-1, Tg(Wnt1-cre)2Sor, mKIAA4009, transcription factor E2F1
Species: mouse
Products:     E2f1

Top Publications

  1. Dagnino L, Fry C, Bartley S, Farnham P, Gallie B, Phillips R. Expression patterns of the E2F family of transcription factors during murine epithelial development. Cell Growth Differ. 1997;8:553-63 pubmed
    ..Thus, selective regulation of E2F forms occurs during murine epithelial development, irrespective of the ectodermal or endodermal origin of such epithelia. ..
  2. Li F, Zhu J, Tessem J, Beilke J, Varella Garcia M, Jensen J, et al. The development of diabetes in E2f1/E2f2 mutant mice reveals important roles for bone marrow-derived cells in preventing islet cell loss. Proc Natl Acad Sci U S A. 2003;100:12935-40 pubmed
    Our studies of mice deficient for the E2F1 and E2F2 transcription factors have revealed essential roles for these proteins in the cell cycle control of pancreatic exocrine cells and the regulation of pancreatic beta cell maintenance...
  3. Cloud J, Rogers C, Reza T, Ziebold U, Stone J, Picard M, et al. Mutant mouse models reveal the relative roles of E2F1 and E2F3 in vivo. Mol Cell Biol. 2002;22:2663-72 pubmed
    The E2F1, -2, and -3 transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor that drive expression of proliferation-associated genes...
  4. Chen D, Opavsky R, Pacal M, Tanimoto N, Wenzel P, Seeliger M, et al. Rb-mediated neuronal differentiation through cell-cycle-independent regulation of E2f3a. PLoS Biol. 2007;5:e179 pubmed
    ..These data reveal a mechanism through which Rb regulates neural differentiation directly, and, unexpectedly, it involves inhibition of E2f3a, not potentiation of tissue-specific factors. ..
  5. Palacios G, Talos F, Nemajerova A, Moll U, Petrenko O. E2F1 plays a direct role in Rb stabilization and p53-independent tumor suppression. Cell Cycle. 2008;7:1776-81 pubmed
    To better understand the role of E2F1 in tumor formation, we analyzed spontaneous tumorigenesis in p53(-/-)E2F1(+/+) and p53(-/-)E2F1(-/-) mice...
  6. Sáenz Robles M, Markovics J, Chong J, Opavsky R, Whitehead R, Leone G, et al. Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2. J Virol. 2007;81:13191-9 pubmed
    ..proliferation is reduced in mice lacking either E2F2 alone or both E2F2 and E2F3a, but not in mice lacking E2F1. These studies support a model in which T antigen eliminates Rb-E2F repressive complexes so that specific activator ..
  7. Black E, Hallstrom T, Dressman H, West M, Nevins J. Distinctions in the specificity of E2F function revealed by gene expression signatures. Proc Natl Acad Sci U S A. 2005;102:15948-53 pubmed
    ..Both E2F1 and E2F3 proteins have been shown to be particularly important for cell proliferation, whereas the E2F1 protein has ..
  8. Pohlers M, Truss M, Frede U, Scholz A, Strehle M, Kuban R, et al. A role for E2F6 in the restriction of male-germ-cell-specific gene expression. Curr Biol. 2005;15:1051-7 pubmed
    ..Like other E2Fs, E2F6 binds to E2F consensus sites, but in contrast to E2F1-5, it lacks an Rb binding domain and functions as an Rb-independent transcriptional repressor [2, 3, 4 and 5]...
  9. Sahin F, Sladek T. E2F-1 has dual roles depending on the cell cycle. Int J Biol Sci. 2010;6:116-28 pubmed

More Information


  1. Li F, Zhu J, Hogan C, DeGregori J. Defective gene expression, S phase progression, and maturation during hematopoiesis in E2F1/E2F2 mutant mice. Mol Cell Biol. 2003;23:3607-22 pubmed
    ..We show that the combined loss of E2F1 and E2F2 in mice leads to profound cell-autonomous defects in the hematopoietic development of multiple cell ..
  2. Wells J, Boyd K, Fry C, Bartley S, Farnham P. Target gene specificity of E2F and pocket protein family members in living cells. Mol Cell Biol. 2000;20:5797-807 pubmed
  3. Chen Q, Hung F, Fromm L, Overbeek P. Induction of cell cycle entry and cell death in postmitotic lens fiber cells by overexpression of E2F1 or E2F2. Invest Ophthalmol Vis Sci. 2000;41:4223-31 pubmed
    ..Human E2F1 and E2F2 cDNAs were linked to the alphaA-crystallin promoter. Transgenic mice were generated by microinjection...
  4. Lazzerini Denchi E, Helin K. E2F1 is crucial for E2F-dependent apoptosis. EMBO Rep. 2005;6:661-8 pubmed
    ..Apoptosis induced by E2F3 is associated with the accumulation of E2F1 and, strikingly, we found that E2F3-induced apoptosis is dependent on E2F1...
  5. Nahle Z, Polakoff J, Davuluri R, McCurrach M, Jacobson M, Narita M, et al. Direct coupling of the cell cycle and cell death machinery by E2F. Nat Cell Biol. 2002;4:859-64 pubmed
    ..The data also underscore how cell cycle progression can be coupled to the apoptotic machinery. ..
  6. Chen Q, Ash J, Branton P, Fromm L, Overbeek P. Inhibition of crystallin expression and induction of apoptosis by lens-specific E1A expression in transgenic mice. Oncogene. 2002;21:1028-37 pubmed
  7. Blanchet E, Annicotte J, Lagarrigue S, Aguilar V, Clapé C, Chavey C, et al. E2F transcription factor-1 regulates oxidative metabolism. Nat Cell Biol. 2011;13:1146-52 pubmed publisher
    ..In pancreatic ?-cells, E2F1 gene regulation facilitated glucose-stimulated insulin secretion...
  8. Leone G, Sears R, Huang E, Rempel R, Nuckolls F, Park C, et al. Myc requires distinct E2F activities to induce S phase and apoptosis. Mol Cell. 2001;8:105-13 pubmed
    Previous work has shown that the Myc transcription factor induces transcription of the E2F1, E2F2, and E2F3 genes...
  9. Murga M, Fernandez Capetillo O, Field S, Moreno B, Borlado L, Fujiwara Y, et al. Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity. Immunity. 2001;15:959-70 pubmed
    ..Rather than functioning as a transcriptional activator, E2F2 appears to function as a transcriptional repressor of genes required for normal S phase entry, particularly E2F1.
  10. Yamasaki L, Bronson R, Williams B, Dyson N, Harlow E, Jacks T. Loss of E2F-1 reduces tumorigenesis and extends the lifespan of Rb1(+/-)mice. Nat Genet. 1998;18:360-4 pubmed
    ..Previously, we reported that loss of E2f1 in mice results in tissue-specific tumour induction and tissue atrophy, demonstrating that E2F-1 normally controls ..
  11. Chong J, Wenzel P, Sáenz Robles M, Nair V, Ferrey A, Hagan J, et al. E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells. Nature. 2009;462:930-4 pubmed publisher
    ..protein (Rb) functions to restrict cells from entering S phase by binding and sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ultimate effectors of a transcriptional program that commit ..
  12. Liu Y, Zacksenhaus E. E2F1 mediates ectopic proliferation and stage-specific p53-dependent apoptosis but not aberrant differentiation in the ocular lens of Rb deficient fetuses. Oncogene. 2000;19:6065-73 pubmed
    ..Mutant mouse embryos lacking Rb exhibit ectopic proliferation and apoptosis that are mediated in some tissues by E2F1, a major partner of Rb, and by the p53 tumor suppressor...
  13. Chen D, Chen Y, Forrest D, Bremner R. E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3. Cell Death Differ. 2013;20:931-40 pubmed publisher
    The 'activating' E2fs (E2f1-3) are transcription factors that potently induce quiescent cells to divide...
  14. Muller H, Helin K. The E2F transcription factors: key regulators of cell proliferation. Biochim Biophys Acta. 2000;1470:M1-12 pubmed
    ..We will discuss the relevance of a thorough understanding of E2F function for cancer therapy. ..
  15. Tsai K, Hu Y, Macleod K, Crowley D, Yamasaki L, Jacks T. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol Cell. 1998;2:293-304 pubmed
    ..0 with anemia and defective skeletal muscle and lung development, demonstrating that E2F-1 regulation is not the sole function of pRB in development. ..
  16. Opavsky R, Tsai S, Guimond M, Arora A, Opavska J, Becknell B, et al. Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis. Proc Natl Acad Sci U S A. 2007;104:15400-5 pubmed
    ..bitransgenic mouse model of Myc-induced T cell lymphomagenesis and analyzed tumor progression in mice deficient for E2f1, E2f2, or E2f3...
  17. Chong J, Tsai S, Sharma N, Opavsky R, Price R, Wu L, et al. E2f3a and E2f3b contribute to the control of cell proliferation and mouse development. Mol Cell Biol. 2009;29:414-24 pubmed publisher
    ..was sufficient to support E2F target gene expression and cell proliferation in the absence of other E2F activators, E2f1 and E2f2, suggesting that these isoforms have redundant functions...
  18. Lu Z, Marcelin G, Bauzon F, Wang H, Fu H, Dun S, et al. pRb is an obesity suppressor in hypothalamus and high-fat diet inhibits pRb in this location. EMBO J. 2013;32:844-57 pubmed publisher
    ..These defects can be corrected by combined deletion of E2f1. In contrast, deleting Rb1 in the antagonizing AGRP/NPY neurons shows no effects...
  19. Wenzel P, Chong J, Sáenz Robles M, Ferrey A, Hagan J, Gomez Y, et al. Cell proliferation in the absence of E2F1-3. Dev Biol. 2011;351:35-45 pubmed publisher
    ..in cultured mouse embryonic fibroblasts that concomitant loss of three E2F activators with overlapping functions (E2F1, E2F2, and E2F3) triggered the p53-p21(Cip1) response and caused cell cycle arrest...
  20. Hsieh M, Das D, Sambandam N, Zhang M, Nahle Z. Regulation of the PDK4 isozyme by the Rb-E2F1 complex. J Biol Chem. 2008;283:27410-7 pubmed publisher
    Loss of the transcription factor E2F1 elicits a complex metabolic phenotype in mice underscored by reduced adiposity and protection from high fat diet-induced diabetes...
  21. Baudino T, Maclean K, Brennan J, Parganas E, Yang C, Aslanian A, et al. Myc-mediated proliferation and lymphomagenesis, but not apoptosis, are compromised by E2f1 loss. Mol Cell. 2003;11:905-14 pubmed
    Myc and E2f1 promote cell cycle progression, but overexpression of either can trigger p53-dependent apoptosis...
  22. Field S, Tsai F, Kuo F, Zubiaga A, Kaelin W, Livingston D, et al. E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell. 1996;85:549-61 pubmed
    ..These findings suggest that while certain members of the E2F family may positively regulate cell cycle progression, E2F-1 functions to regulate apoptosis and to suppress cell proliferation. ..
  23. Iglesias A, Murga M, Laresgoiti U, Skoudy A, Bernales I, Fullaondo A, et al. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice. J Clin Invest. 2004;113:1398-407 pubmed
    ..Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo...
  24. Tsai S, Opavsky R, Sharma N, Wu L, Naidu S, Nolan E, et al. Mouse development with a single E2F activator. Nature. 2008;454:1137-41 pubmed publisher
    ..To begin to evaluate this genetic complexity, we targeted the inactivation of the entire subset of activators, E2f1, E2f2, E2f3a and E2f3b, singly or in combination in mice...
  25. Yamasaki L, Jacks T, Bronson R, Goillot E, Harlow E, Dyson N. Tumor induction and tissue atrophy in mice lacking E2F-1. Cell. 1996;85:537-48 pubmed
    ..Although overexpression of E2F-1 in tissue culture cells can stimulate cell proliferation and be oncogenic, loss of E2F-1 in mice results in tumorigenesis, demonstrating that E2F-1 also functions as a tumor suppressor. ..
  26. Wikonkal N, Remenyik E, Knezevic D, Zhang W, Liu M, Zhao H, et al. Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice. Nat Cell Biol. 2003;5:655-60 pubmed
    The E2f1 transcription factor, which regulates genes required for S-phase entry, also induces apoptosis by transcriptional and post-translational mechanisms...
  27. Lin S, Skapek S, Papermaster D, Hankin M, Lee E. The proliferative and apoptotic activities of E2F1 in the mouse retina. Oncogene. 2001;20:7073-84 pubmed
    The E2F1 transcription factor controls cell proliferation and apoptosis. E2F1 activity is negatively regulated by the retinoblastoma (RB) protein...
  28. Fajas L, Annicotte J, Miard S, Sarruf D, Watanabe M, Auwerx J. Impaired pancreatic growth, beta cell mass, and beta cell function in E2F1 (-/- )mice. J Clin Invest. 2004;113:1288-95 pubmed
    We evaluated the effects of E2F1 on glucose homeostasis using E2F1(-/-) mice. E2F1(-/-) mice show an overall reduction in pancreatic size as the result of impaired postnatal pancreatic growth...
  29. Wang Z, Yang H, Livingston D. Endogenous E2F-1 promotes timely G0 exit of resting mouse embryo fibroblasts. Proc Natl Acad Sci U S A. 1998;95:15583-6 pubmed
    ..Therefore, E2F-1 exerts a unique function leading to timely G0 exit of resting cultured primary cells, while at the same time being unnecessary for normal G1 to S phase progression of cycling cells. ..
  30. de la Luna S, Burden M, Lee C, La Thangue N. Nuclear accumulation of the E2F heterodimer regulated by subunit composition and alternative splicing of a nuclear localization signal. J Cell Sci. 1996;109 ( Pt 10):2443-52 pubmed
    ..These data define a new level of control in the E2F transcription factor whereby interplay between subunits dictates the levels of nuclear DNA binding activity. ..
  31. Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev. 1998;12:2245-62 pubmed
  32. Sharma N, Timmers C, Trikha P, Saavedra H, Obery A, Leone G. Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 is essential for G1/S progression and cellular transformation. J Biol Chem. 2006;281:36124-31 pubmed
    ..Previous work has demonstrated that the targeted inactivation of E2f1, E2f2, and E2f3 results in elevated p21(CIP1) protein levels, loss of E2F target gene expression, and cell cycle ..
  33. Timmers C, Sharma N, Opavsky R, Maiti B, Wu L, Wu J, et al. E2f1, E2f2, and E2f3 control E2F target expression and cellular proliferation via a p53-dependent negative feedback loop. Mol Cell Biol. 2007;27:65-78 pubmed
    ..gene-targeting approach, we show that the targeted disruption of the entire E2F activator subclass composed of E2f1, E2f2, and E2f3 in mouse embryonic fibroblasts leads to the activation of p53 and the induction of p53 target genes,..
  34. Wells J, Graveel C, Bartley S, Madore S, Farnham P. The identification of E2F1-specific target genes. Proc Natl Acad Sci U S A. 2002;99:3890-5 pubmed
    ..To investigate this possibility further, we have analyzed gene expression in E2F1 nullizygous mice...
  35. Halaban R, Cheng E, Zhang Y, Mandigo C, Miglarese M. Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1. Oncogene. 1998;16:2489-501 pubmed
    ..of gene disruption and ectopic expression in growth factor-dependent mouse melanocytes, we studied the roles of E2F1 and the p16INK4A and p21WAF1/CIP1 CKIs (cyclin dependent kinase inhibitors) in the acquisition of TPA (12-O-..
  36. Cooper Kuhn C, Vroemen M, Brown J, Ye H, Thompson M, Winkler J, et al. Impaired adult neurogenesis in mice lacking the transcription factor E2F1. Mol Cell Neurosci. 2002;21:312-23 pubmed
    ..Here, we demonstrate that the transcription factor E2F1, which is targeted by several signaling cascades that are activated by growth factors, is involved in ..
  37. Helin K, Wu C, Fattaey A, Lees J, Dynlacht B, Ngwu C, et al. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation. Genes Dev. 1993;7:1850-61 pubmed
    ..We suggest that "E2F" is the activity that is formed when an E2F-1-related protein and a DP-1-related protein dimerize. ..
  38. Wu L, Timmers C, Maiti B, Saavedra H, Sang L, Chong G, et al. The E2F1-3 transcription factors are essential for cellular proliferation. Nature. 2001;414:457-62 pubmed
    ..b>E2F1, E2F2 and E2F3 belong to a subclass of E2F factors thought to act as transcriptional activators important for ..
  39. Wloga E, Criniti V, Yamasaki L, Bronson R. Lymphomagenesis and female-specific lethality in p53-deficient mice occur independently of E2f1. Nat Cell Biol. 2004;6:565-7; author reply 567-8 pubmed
  40. Matsumura I, Tanaka H, Kanakura Y. E2F1 and c-Myc in cell growth and death. Cell Cycle. 2003;2:333-8 pubmed
    ..For example, overexpression of c-Myc or E2F1, which are involved in G1/S transition, causes apoptosis under certain conditions...
  41. Saavedra H, Wu L, de Bruin A, Timmers C, Rosol T, Weinstein M, et al. Specificity of E2F1, E2F2, and E2F3 in mediating phenotypes induced by loss of Rb. Cell Growth Differ. 2002;13:215-25 pubmed
    The Rb/E2F pathway plays a critical role in the control ofcellular proliferation. Here, we report that E2F1, E2F2, and E2F3 make major individual contributions toward the in vivo phenotypic consequences of Rb deficiency...
  42. Yang M, Wu S, Jia J, May W. JAZ mediates G1 cell cycle arrest by interacting with and inhibiting E2F1. Cell Cycle. 2011;10:2390-9 pubmed
    ..negatively regulate the cell cycle in a novel, p53-independent mechanism resulting from the direct interaction with E2F1, a key intermediate in regulating cell proliferation and tumor suppression...
  43. de Bruin A, Maiti B, Jakoi L, Timmers C, Buerki R, Leone G. Identification and characterization of E2F7, a novel mammalian E2F family member capable of blocking cellular proliferation. J Biol Chem. 2003;278:42041-9 pubmed
    ..Like the expression of the known E2F activators, E2F1, E2F2, and E2F3, the expression of E2F7 is growth-regulated, at least in part, through E2F binding elements on its ..
  44. Zhu J, Field S, Gore L, Thompson M, Yang H, Fujiwara Y, et al. E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis. Mol Cell Biol. 2001;21:8547-64 pubmed
    E2F activity is critical for the control of the G(1) to S phase transition. We show that the combined loss of E2F1 and E2F2 results in profound effects on hematopoietic cell proliferation and differentiation, as well as increased ..
  45. Maiti B, Li J, de Bruin A, Gordon F, Timmers C, Opavsky R, et al. Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferation. J Biol Chem. 2005;280:18211-20 pubmed
    ..evidence in the field, mammalian E2Fs can be functionally categorized into either transcriptional activators (E2F1, E2F2, and E2F3a) or repressors (E2F3b, E2F4, E2F5, E2F6, and E2F7)...
  46. Holmberg C, Helin K, Sehested M, Karlstrom O. E2F-1-induced p53-independent apoptosis in transgenic mice. Oncogene. 1998;17:143-55 pubmed
    ..Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered testicular atrophy. ..
  47. Annicotte J, Blanchet E, Chavey C, Iankova I, Costes S, Assou S, et al. The CDK4-pRB-E2F1 pathway controls insulin secretion. Nat Cell Biol. 2009;11:1017-23 pubmed publisher
    CDK4-pRB-E2F1 cell-cycle regulators are robustly expressed in non-proliferating beta cells, suggesting that besides the control of beta-cell number the CDK4-pRB-E2F1 pathway has a role in beta-cell function...
  48. Yang X, Sladek T. Novel phosphorylated forms of E2F-1 transcription factor bind to the retinoblastoma protein in cells overexpressing an E2F-1 cDNA. Biochem Biophys Res Commun. 1997;232:336-9 pubmed
  49. Fajas L, Landsberg R, Huss Garcia Y, Sardet C, Lees J, Auwerx J. E2Fs regulate adipocyte differentiation. Dev Cell. 2002;3:39-49 pubmed
    ..We show here that E2F1 induces PPAR gamma transcription during clonal expansion, whereas E2F4 represses PPARg amma expression during ..
  50. Strachan G, Kopp A, Koike M, Morgan K, Jordan Sciutto K. Chemokine- and neurotrophic factor-induced changes in E2F1 localization and phosphorylation of the retinoblastoma susceptibility gene product (pRb) occur by distinct mechanisms in murine cortical cultures. Exp Neurol. 2005;193:455-68 pubmed
    The retinoblastoma susceptibility gene product (pRb) and E2F1 have been found to exhibit altered localization and increased staining in several neurodegenerative diseases...
  51. Bartley S, Szakaly R, Farnham P. Characterization of the 3' untranslated region of mouse E2F1 mRNA. Gene. 1998;223:355-60 pubmed
    ..We have focused on characterizing the cell cycle stage-specific expression of one family member, E2F1. Previous studies indicated that there are two mouse E2F1 (mE2F1) mRNA species whose abundance peaks in early S ..
  52. Ghanem N, Andrusiak M, Svoboda D, Al Lafi S, Julian L, McClellan K, et al. The Rb/E2F pathway modulates neurogenesis through direct regulation of the Dlx1/Dlx2 bigene cluster. J Neurosci. 2012;32:8219-30 pubmed publisher
  53. Chen H, Ouseph M, Li J, Pécot T, Chokshi V, Kent L, et al. Canonical and atypical E2Fs regulate the mammalian endocycle. Nat Cell Biol. 2012;14:1192-202 pubmed publisher
    ..cre mice we identified two opposing arms of the E2F program, one driven by canonical transcription activation (E2F1, E2F2 and E2F3) and the other by atypical repression (E2F7 and E2F8), that converge on the regulation of endocycles ..
  54. Berman S, Yuan T, Miller E, Lee E, Caron A, Lees J. The retinoblastoma protein tumor suppressor is important for appropriate osteoblast differentiation and bone development. Mol Cancer Res. 2008;6:1440-51 pubmed publisher
    ..we show that the cell cycle and the bone defects in Rb-deficient embryos can be suppressed by deletion of E2f1, a known proliferation inducer that acts downstream of Rb...
  55. Cartier J, Berthelet J, Marivin A, Gemble S, Edmond V, Plenchette S, et al. Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin transcription. J Biol Chem. 2011;286:26406-17 pubmed publisher
    ..Here, we show that the N-terminal part of cIAP1 directly interacts with the DNA binding domain of the E2F1 transcription factor...
  56. Ivanova I, Dagnino L. Activation of p38- and CRM1-dependent nuclear export promotes E2F1 degradation during keratinocyte differentiation. Oncogene. 2007;26:1147-54 pubmed
    ..We have shown that differentiation in primary epidermal keratinocytes leads to E2F1 downregulation via activation of protein kinase C and p38 mitogen-activated protein kinase...