e2f2 transcription factor


Summary: An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A. E2F2 activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis.

Top Publications

  1. Iglesias Ara A, Zenarruzabeitia O, Fernandez Rueda J, Sánchez Tilló E, Field S, Celada A, et al. Accelerated DNA replication in E2F1- and E2F2-deficient macrophages leads to induction of the DNA damage response and p21(CIP1)-dependent senescence. Oncogene. 2010;29:5579-90 pubmed publisher
    ..Our data indicate that their absence in differentiating macrophages initiates a senescence program that results from enforcement of a DNA damage response triggered by DNA hyper-replication. ..
  2. Frolov M, Moon N, Dyson N. dDP is needed for normal cell proliferation. Mol Cell Biol. 2005;25:3027-39 pubmed
    ..Thus, dDP is not essential for developmental control of the G1-to-S transition, but it is required for normal cell proliferation, for optimal DNA synthesis, and for efficient G2/M progression. ..
  3. 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
    ..These findings suggest that a critical function of the E2F1, E2F2, and E2F3 activators is in the control of a p53-dependent axis that indirectly regulates E2F-mediated transcriptional repression and cellular proliferation. ..
  4. 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
    ..By targeting the entire subclass of E2F transcriptional activators we provide direct genetic evidence for their essential role in cell cycle progression, proliferation and development. ..
  5. 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
    ..Consistent with these observations, E2F1/E2F2 mutant mice are highly predisposed to the development of tumors, and some mice exhibit signs of autoimmunity. ..
  6. Frolov M, Huen D, Stevaux O, Dimova D, Balczarek Strang K, Elsdon M, et al. Functional antagonism between E2F family members. Genes Dev. 2001;15:2146-60 pubmed
    ..This study shows how repressor and activator E2Fs are used to pattern transcription and how the net effect of E2F on cell proliferation results from the interplay between two types of E2F complexes that have antagonistic functions. ..
  7. 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
    ..These observations, together with the fact that E2F7 and E2F8 can homodimerize and are expressed in the same adult tissues, suggest that they may have overlapping and perhaps synergistic roles in the control of cellular proliferation. ..
  8. 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
    ..These studies support a model in which T antigen eliminates Rb-E2F repressive complexes so that specific activator E2Fs can drive S-phase entry...
  9. 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
    ..This work contextualizes the activator versus repressor functions of E2f1-3 in vivo, revealing distinct roles in dividing versus differentiating cells and in normal versus cancer-like cell cycles. ..

More Information


  1. Bueno M, Gómez de Cedrón M, Laresgoiti U, Fernandez Piqueras J, Zubiaga A, Malumbres M. Multiple E2F-induced microRNAs prevent replicative stress in response to mitogenic signaling. Mol Cell Biol. 2010;30:2983-95 pubmed publisher
    ..Given the known function of E2F of inducing other oncogenic miRNAs, control of miRNAs by E2F is likely to play multiple roles in cell proliferation and in proliferative diseases such as cancer. ..
  2. Ginsberg D, Vairo G, Chittenden T, Xiao Z, Xu G, Wydner K, et al. E2F-4, a new member of the E2F transcription factor family, interacts with p107. Genes Dev. 1994;8:2665-79 pubmed
    ..p107 binding not only can be linked to the regulation of E2F-4 transcriptional activity, but also to suppression of the ability of E2F-4 to transform an immortalized rodent cell line. ..
  3. Okamoto O, Oba Shinjo S, Lopes L, Nagahashi Marie S. Expression of HOXC9 and E2F2 are up-regulated in CD133(+) cells isolated from human astrocytomas and associate with transformation of human astrocytes. Biochim Biophys Acta. 2007;1769:437-42 pubmed
    ..Due to their distinctive expression in CD133(+) cells, the use of E2F2 and HOXC9 as therapeutic targets for tumor eradication is suggested. ..
  4. 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
    ..These results suggest that the negative regulation of the p53-p21(CIP1) axis by the E2F1-3 factors is critical for cell cycle progression and cellular transformation. ..
  5. McAlister J, Joyce N, Harris D, Ali R, Larkin D. Induction of replication in human corneal endothelial cells by E2F2 transcription factor cDNA transfer. Invest Ophthalmol Vis Sci. 2005;46:3597-603 pubmed
    ..Overexpression of the transcription factor E2F2 in nonmitotic human corneal endothelial cells results in short-term expression, cell-cycle progression, and increased monolayer cell density. ..
  6. 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
    ..These findings provide a molecular basis for the observed specificity among E2F activators during development. ..
  7. Fogal V, Kartasheva N, Trigiante G, Llanos S, Yap D, Vousden K, et al. ASPP1 and ASPP2 are new transcriptional targets of E2F. Cell Death Differ. 2005;12:369-76 pubmed
    ..The identification of ASPP1 and ASPP2 genes as transcriptional targets of E2F provides another mechanism by which E2F cooperates with p53 to induce apoptosis. ..
  8. Lees J, Saito M, Vidal M, Valentine M, Look T, Harlow E, et al. The retinoblastoma protein binds to a family of E2F transcription factors. Mol Cell Biol. 1993;13:7813-25 pubmed
    ..These observations suggest that the E2F activities described previously result from the combined action of a family of proteins. ..
  9. Moberg K, Starz M, Lees J. E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry. Mol Cell Biol. 1996;16:1436-49 pubmed
    ..Despite this, a considerable amount of E2F-4 exists as free E2F. In G1 cells, this accounts for almost all of the free activity. Once the cells enter S phase, free E2F is composed of an equal mixture of E2F-4 and E2F-1. ..
  10. Truscott M, Harada R, Vadnais C, Robert F, Nepveu A. p110 CUX1 cooperates with E2F transcription factors in the transcriptional activation of cell cycle-regulated genes. Mol Cell Biol. 2008;28:3127-38 pubmed publisher
    ..Reporter assays on a subset of common targets confirmed that p110 CUX1 and E2F1 cooperate in their transcriptional activation. Overall, our results show that p110 CUX1 and E2F1 cooperate in the regulation of many cell cycle genes. ..
  11. Gill R, Hamel P. Subcellular compartmentalization of E2F family members is required for maintenance of the postmitotic state in terminally differentiated muscle. J Cell Biol. 2000;148:1187-201 pubmed
    ..These data demonstrate that regulation of the subcellular compartmentalization of E2F-family members is required to maintain nuclei in a quiescent state in terminally differentiated cells. ..
  12. 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
    ..These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult. ..
  13. 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
    ..These results identify the E2f2 locus as a tumor suppressor through its ability to modulate apoptosis. ..
  14. Dirlam A, Spike B, Macleod K. Deregulated E2f-2 underlies cell cycle and maturation defects in retinoblastoma null erythroblasts. Mol Cell Biol. 2007;27:8713-28 pubmed
    ..The identification of a tissue-restricted role for E2f-2 in erythropoiesis highlights the nonredundant nature of E2f transcription factor activities in cell growth and differentiation...
  15. Ambrus A, Nicolay B, Rasheva V, Suckling R, Frolov M. dE2F2-independent rescue of proliferation in cells lacking an activator dE2F1. Mol Cell Biol. 2007;27:8561-70 pubmed
    ..Thus, mutation of bel relieves the dE2F2-mediated cell cycle arrest in de2f1 mutant cells through a novel Ci155-dependent mechanism without functional inactivation of the dE2F2 repressor. ..
  16. 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
    ..Together, these data implicate E2F1-3 in mediating transcriptional repression by Rb during cell cycle exit and point to a critical role for their repressive functions in cell survival. ..
  17. Schlisio S, Halperin T, Vidal M, Nevins J. Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function. EMBO J. 2002;21:5775-86 pubmed
    ..We suggest that the ability of RYBP to mediate an interaction between E2F2 or E2F3 and YY1 is an important component of Cdc6 activation and provides a basis for specificity of E2F function. ..
  18. 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
    ..These results provide clear evidence for functional specificity among E2Fs in the control of Rb-dependent proliferation and apoptosis in a tissue-specific manner. ..
  19. DeGregori J. The genetics of the E2F family of transcription factors: shared functions and unique roles. Biochim Biophys Acta. 2002;1602:131-50 pubmed
  20. Infante A, Laresgoiti U, Fernández Rueda J, Fullaondo A, Galan J, Diaz Uriarte R, et al. E2F2 represses cell cycle regulators to maintain quiescence. Cell Cycle. 2008;7:3915-27 pubmed
    ..We conclude that E2F2 functions to transcriptionally repress cell cycle genes to establish the G(0) state. ..
  21. Enos M, Bancos S, Bushnell T, Crispe I. E2F4 modulates differentiation and gene expression in hematopoietic progenitor cells during commitment to the lymphoid lineage. J Immunol. 2008;180:3699-707 pubmed
    ..However, we did not detect effects on cell proliferation. These findings emphasize the significance of E2F4 in controlling gene expression and cell fate. ..
  22. Osinalde N, Olea M, Mitxelena J, Aloria K, Rodriguez J, Fullaondo A, et al. The nuclear protein ALY binds to and modulates the activity of transcription factor E2F2. Mol Cell Proteomics. 2013;12:1087-98 pubmed publisher
    ..We show that ALY influences the expression of more than 400 genes, including 98 genes bearing consensus E2F motifs. Thus, ALY emerges as a novel E2F2-interacting protein and a relevant modulator of E2F-responsive gene expression. ..
  23. 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. ..
  24. Zhou J, Zhu Y, Cheng M, Dinesh D, Thorne T, Poh K, et al. Regulation of vascular contractility and blood pressure by the E2F2 transcription factor. Circulation. 2009;120:1213-21 pubmed publisher
    ..Our results identify a cell-cycle-independent mechanism by which E2F2 regulates endothelial function, arterial contractility, and blood pressure. ..
  25. 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. ..
  26. Strom D, Cleveland J, Chellappan S, Nip J, Hiebert S. E2F-1 and E2F-3 are functionally distinct in their ability to promote myeloid cell cycle progression and block granulocyte differentiation. Cell Growth Differ. 1998;9:59-69 pubmed
    ..Therefore, E2F-1, but not E2F-3, can temporally replace the requirement for growth factors to promote cell cycle progression, and in terminally differentiating cells, this leads to a block in differentiation and induction of apoptosis. ..
  27. Tao T, Shen Q, Luo J, Xu Y, Liang W. MicroRNA-125a Regulates Cell Proliferation Via Directly Targeting E2F2 in Osteosarcoma. Cell Physiol Biochem. 2017;43:768-774 pubmed publisher
    ..Our results suggest that miR-125a acts as a tumor suppressor via regulation of E2F2 expression in osteosarcoma progression, and miR-125a may represent a novel therapeutic target for the treatment of osteosarcoma. ..
  28. Pilon A, Arcasoy M, Dressman H, Vayda S, Maksimova Y, Sangerman J, et al. Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2. Mol Cell Biol. 2008;28:7394-401 pubmed publisher
    ..We propose a model in which EKLF-dependent activation and modification of the E2f2 locus is required for cell cycle progression preceding terminal erythroid differentiation. ..
  29. Kim S, Kim A, Jeong J, Choi J, Kweon H. 4-hexylresorcinol stimulates the differentiation of SCC-9 cells through the suppression of E2F2, E2F3 and Sp3 expression and the promotion of Sp1 expression. Oncol Rep. 2012;28:677-81 pubmed publisher
    ..Together, our results indicate that 4-HR induces the differentiation of SCC-9 via the modulation of the E2F-mediated signaling pathway. ..
  30. Wang P, Chen S, Fang H, Wu X, Chen D, Peng L, et al. miR-214/199a/199a* cluster levels predict poor survival in hepatocellular carcinoma through interference with cell-cycle regulators. Oncotarget. 2016;7:929-45 pubmed publisher
    ..Our results demonstrate that miR-214 has tumor-suppressive activity in HCC through inhibition of E2F2, CDK3 and CDK6. ..
  31. Sawado T, Yamaguchi M, Nishimoto Y, Ohno K, Sakaguchi K, Matsukage A. dE2F2, a novel E2F-family transcription factor in Drosophila melanogaster. Biochem Biophys Res Commun. 1998;251:409-15 pubmed
    ..Furthermore, cotransfection experiments in Kc cells demonstrated dE2F2 repression of the PCNA gene promoter activity, while dE2F caused activation, the target site for the repression being identical to the dE2F-recognition site. ..
  32. Berns K, Hijmans E, Koh E, Daley G, Bernards R. A genetic screen to identify genes that rescue the slow growth phenotype of c-myc null fibroblasts. Oncogene. 2000;19:3330-4 pubmed
    ..Our data support the notion that there are no functional equivalents of the myc family of proto-oncogenes and also suggest that there are no c-Myc-activated genes that alone can substitute for c-Myc in control of cell proliferation. ..
  33. Conner E, Lemmer E, Omori M, Wirth P, Factor V, Thorgeirsson S. Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis. Oncogene. 2000;19:5054-62 pubmed
    ..In conclusion, E2F-1 overexpression in the liver causes dysplasia and tumors and suggests a cooperation between E2F-1 and c-myc oncogenes during liver oncogenesis. ..
  34. Scheijen B, Bronk M, van der Meer T, de Jong D, Bernards R. High incidence of thymic epithelial tumors in E2F2 transgenic mice. J Biol Chem. 2004;279:10476-83 pubmed
    ..Interestingly, Emu-pp-E2F1 mice do not display cortical thymomas. These data argue that E2F2 promotes unscheduled cell division and oncogenic transformation of thymic epithelial cells. ..
  35. Santoni Rugiu E, Jensen M, Thorgeirsson S. 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. Cancer Res. 1998;58:123-34 pubmed
    ..The data suggest that coexpression of c-myc and TGF-alpha leads to a selective growth advantage for hepatic (pre)neoplastic cells by disrupting the pRb/E2F pathway and by TGF-alpha-mediated reduction of apoptosis. ..
  36. Dirks P, Rutka J, Hubbard S, Mondal S, Hamel P. The E2F-family proteins induce distinct cell cycle regulatory factors in p16-arrested, U343 astrocytoma cells. Oncogene. 1998;17:867-76 pubmed
    ..While overcoming this cell cycle block, each of the E2F's uniquely affect the expression of a number of cell cycle regulatory proteins and have distinct abilities to promote cell death. ..
  37. Stevaux O, Dimova D, Frolov M, Taylor Harding B, Morris E, Dyson N. Distinct mechanisms of E2F regulation by Drosophila RBF1 and RBF2. EMBO J. 2002;21:4927-37 pubmed
    ..These results suggest that there is a remarkable degree of symmetry in the arrangement of E2F and RB family members in mammalian cells and in DROSOPHILA. ..
  38. Bilousova G, Marusyk A, Porter C, Cardiff R, DeGregori J. Impaired DNA replication within progenitor cell pools promotes leukemogenesis. PLoS Biol. 2005;3:e401 pubmed
  39. 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
    ..These results provide in vivo evidence for a direct role of E2F family members in regulating non-traditional cell cycles in mammals. ..
  40. Won J, Yim J, Kim T. Opposing regulatory roles of E2F in human telomerase reverse transcriptase (hTERT) gene expression in human tumor and normal somatic cells. FASEB J. 2002;16:1943-5 pubmed
    ..These contrasting effects of E2F transcription factors on the hTERT promoter could underlie the paradoxical biological activities of E2F, which can both promote and inhibit cellular proliferation and tumorigenesis. ..
  41. Zhu Y, Jin K, Mao X, Greenberg D. Vascular endothelial growth factor promotes proliferation of cortical neuron precursors by regulating E2F expression. FASEB J. 2003;17:186-93 pubmed
    ..These findings help to provide a molecular basis for some of the recently identified neuronal effects of VEGF. ..
  42. Wichmann A, Uyetake L, Su T. E2F1 and E2F2 have opposite effects on radiation-induced p53-independent apoptosis in Drosophila. Dev Biol. 2010;346:80-9 pubmed publisher
    ..We conclude that p53-dependent and p53-independent apoptoses show differential reliance on E2F activity in Drosophila. ..
  43. Komatsu Y, Ito I, Wayama M, Fujimura A, Akaogi K, Machida H, et al. PPARgamma ligands suppress the feedback loop between E2F2 and cyclin-E1. Biochem Biophys Res Commun. 2008;370:145-8 pubmed publisher
    ..Thus, we propose that troglitazone suppresses the feedback loop containing E2F2, cyclin-E1, and Rb protein. ..
  44. Chabout M, Cl ment B, Philipps G. S phase and meristem-specific expression of the tobacco RNR1b gene is mediated by an E2F element located in the 5' leader sequence. J Biol Chem. 2002;277:17845-51 pubmed publisher
    ..For the first time in plants, a single E2F motif found in the leader sequence plays an important role in the meristem and S phase-specific expression of the tobacco RNR1b gene...
  45. Kosugi S, Ohashi Y. Interaction of the Arabidopsis E2F and DP proteins confers their concomitant nuclear translocation and transactivation. Plant Physiol. 2002;128:833-43 pubmed
    ..These observations suggest that the function of plant E2F and DP proteins is primarily controlled by their nuclear localization mediated by the interaction with specific partner proteins. ..
  46. Yu B, Lane M, Wadler S. SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells. Biochem Pharmacol. 2002;64:1091-100 pubmed
    ..These findings delineate a previously undescribed mechanism for SU9516-mediated cell growth arrest through down-regulation of cyclin D1, inhibition of cdk2 levels and activity, and pan-sequestration of E2F. ..
  47. Wang H, Shao N, Ding Q, Cui J, Reddy E, Rao V. BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases. Oncogene. 1997;15:143-57 pubmed
  48. Taylor Harding B, Binné U, Korenjak M, Brehm A, Dyson N. p55, the Drosophila ortholog of RbAp46/RbAp48, is required for the repression of dE2F2/RBF-regulated genes. Mol Cell Biol. 2004;24:9124-36 pubmed
  49. Vigo E, Muller H, Prosperini E, Hateboer G, Cartwright P, Moroni M, et al. CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase. Mol Cell Biol. 1999;19:6379-95 pubmed
    ..Taken together, our results provide an important step in defining how E2F activity leads to deregulated proliferation. ..
  50. Funke Kaiser H, Reichenberger F, Köpke K, Herrmann S, Pfeifer J, Orzechowski H, et al. Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation. Hum Mol Genet. 2003;12:423-33 pubmed
    ..This study provides the first evidence of a link between the cell-cycle-associated E2F family and BP regulation via a component of the endothelin system. ..
  51. Kwon M, Nam E, Cho S, Park H, Shin H, Park J, et al. E2F1 expression predicts outcome in Korean women who undergo surgery for breast carcinoma. Ann Surg Oncol. 2010;17:564-71 pubmed publisher
    ..E2F1 may be a potential prognostic and predictive factor for clinical outcome and therapeutic results following adjuvant chemotherapy in HRNBC patients. ..
  52. Lissy N, Davis P, Irwin M, Kaelin W, Dowdy S. A common E2F-1 and p73 pathway mediates cell death induced by TCR activation. Nature. 2000;407:642-5 pubmed
    ..We conclude that TCR-AICD occurs from a late G1 cell-cycle checkpoint that is dependent on both E2F-1 and p73 activities. These observations indicate that, unlike p53, p73 serves to integrate receptor-mediated apoptotic stimuli. ..
  53. Ebelt H, Liu Z, Muller Werdan U, Werdan K, Braun T. Making omelets without breaking eggs: E2F-mediated induction of cardiomyoycte cell proliferation without stimulation of apoptosis. Cell Cycle. 2006;5:2436-9 pubmed
    ..This finding might open a new access to stimulate regeneration in postmitotic tissues such as the heart. ..