e2f5 transcription factor


Summary: An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F5 recruits chromatin remodeling factors indirectly to target gene promoters through RETINOBLASTOMA LIKE PROTEIN P130.

Top Publications

  1. Macaluso M, Cinti C, Russo G, Russo A, Giordano A. pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-alpha in breast cancer. Oncogene. 2003;22:3511-7 pubmed
  2. 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. ..
  3. Hijmans E, Voorhoeve P, Beijersbergen R, van T Veer L, Bernards R. E2F-5, a new E2F family member that interacts with p130 in vivo. Mol Cell Biol. 1995;15:3082-9 pubmed
    ..E2F-5 resembles the other E2Fs in that it binds to a consensus E2F site in a cooperative fashion with DP-1. By using a specific E2F-5 antiserum, we found that under physiological conditions, E2F-5 interacts preferentially with p130. ..
  4. Chen Q, Liang D, Yang T, Leone G, Overbeek P. Distinct capacities of individual E2Fs to induce cell cycle re-entry in postmitotic lens fiber cells of transgenic mice. Dev Neurosci. 2004;26:435-45 pubmed
    ..E2F3a and E2F4, but not E2F5, function to induce cell cycle entry, although E2F4 has more modest activity. E2F3a may induce cell death primarily through activation of p73alpha. ..
  5. Chen C, Kang Y, Siegel P, Massague J. E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression. Cell. 2002;110:19-32 pubmed
    ..Smad proteins therefore mediate transcriptional activation or repression depending on their associated partners. ..
  6. Gaubatz S, Lindeman G, Ishida S, Jakoi L, Nevins J, Livingston D, et al. E2F4 and E2F5 play an essential role in pocket protein-mediated G1 control. Mol Cell. 2000;6:729-35 pubmed
    ..However, they failed to arrest in G1 in response to p16INK4a. Thus, E2F4 and E2F5 are dispensable for cell cycle progression but necessary for pocket protein-mediated G1 arrest of cycling cells. ..
  7. Furukawa Y, Iwase S, Kikuchi J, Nakamura M, Yamada H, Matsuda M. Transcriptional repression of the E2F-1 gene by interferon-alpha is mediated through induction of E2F-4/pRB and E2F-4/p130 complexes. Oncogene. 1999;18:2003-14 pubmed
    ..Our findings indicate that E2F-4 is a critical regulator of E2F-1, which offer an excellent paradigm for understanding functional diversity within the E2F family. ..
  8. Pierce A, Schneider Broussard R, Philhower J, Johnson D. Differential activities of E2F family members: unique functions in regulating transcription. Mol Carcinog. 1998;22:190-8 pubmed
    ..We found that, consistent with a role for E2F5 in transcriptional repression, E2F5's binding partner p130, like Rb, could also actively repress transcription when directly bound to a target promoter. ..
  9. Dagnino L, Fry C, Bartley S, Farnham P, Gallie B, Phillips R. Expression patterns of the E2F family of transcription factors during mouse nervous system development. Mech Dev. 1997;66:13-25 pubmed
    ..We conclude that individual E2F forms are differentially regulated during the development of distinct tissues, and especially during neuronal development. ..

More Information


  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. Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A, et al. E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. Proc Natl Acad Sci U S A. 1995;92:2403-7 pubmed
    ..These findings suggest that E2F-4 and E2F-5 may contribute to the regulation of early G1 events including the G0/G1 transition. ..
  3. Muller H, Moroni M, Vigo E, Petersen B, Bartek J, Helin K. Induction of S-phase entry by E2F transcription factors depends on their nuclear localization. Mol Cell Biol. 1997;17:5508-20 pubmed
  4. Karlseder J, Rotheneder H, Wintersberger E. Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. Mol Cell Biol. 1996;16:1659-67 pubmed
    ..Our data are in line with the hypothesis that E2F functions as a growth- and cell cycle regulated tethering factor between Sp1 and the basic transcription machinery. ..
  5. Apostolova M, Ivanova I, Dagnino C, D Souza S, Dagnino L. Active nuclear import and export pathways regulate E2F-5 subcellular localization. J Biol Chem. 2002;277:34471-9 pubmed
    ..This region excludes the DNA- and the p130-binding domains. Thus, the subcellular distribution of E2F-5 is tightly regulated in intact cells, through multiple functional domains that direct nucleocytoplasmic shuttling of this protein. ..
  6. Lukas J, Petersen B, Holm K, Bartek J, Helin K. Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression. Mol Cell Biol. 1996;16:1047-57 pubmed
    ..Since E2F-4 and E2F-5 cannot promote S-phase entry by themselves, our results may provide an explanation for the apparent lack of aberrations in p107 or p130 in human cancer. ..
  7. Lindeman G, Dagnino L, Gaubatz S, Xu Y, Bronson R, Warren H, et al. A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting. Genes Dev. 1998;12:1092-8 pubmed
    ..Cell cycle kinetics were not perturbed in homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proliferation. Rather, it affects the secretory behavior of a differentiated neural tissue. ..
  8. Ishimoto T, Shiozaki A, Ichikawa D, Fujiwara H, Konishi H, Komatsu S, et al. E2F5 as an independent prognostic factor in esophageal squamous cell carcinoma. Anticancer Res. 2013;33:5415-20 pubmed
    ..In multivariate analysis, the expression of E2F5 was one of the most important independent prognostic factors after radical esophagectomy. The expression of E2F5 in ESCC may be correlated with a worse prognosis of patients with ESCC. ..
  9. Fry C, Slansky J, Farnham P. Position-dependent transcriptional regulation of the murine dihydrofolate reductase promoter by the E2F transactivation domain. Mol Cell Biol. 1997;17:1966-76 pubmed
    ..We propose that, unlike other E2F-regulated promoters, robust transcription from the dhfr promoter requires an E2F transactivation domain close to the transcription start site. ..
  10. Chen Q, Liang D, Overbeek P. Overexpression of E2F5/p130, but not E2F5 alone, can inhibit E2F-induced cell cycle entry in transgenic mice. Mol Vis. 2008;14:602-14 pubmed
    The retinoblastoma (Rb) gene family member p130 binds preferentially to the E2F5 transcription factor and forms a repressive E2F5/p130 complex that inhibits cell cycle progression and tumor growth...
  11. Campanero M, Armstrong M, Flemington E. CpG methylation as a mechanism for the regulation of E2F activity. Proc Natl Acad Sci U S A. 2000;97:6481-6 pubmed
    ..Together, these data illustrate a means through which E2F activity can be controlled. ..
  12. Milton A, Khaire N, Ingram L, O Donnell A, La Thangue N. 14-3-3 proteins integrate E2F activity with the DNA damage response. EMBO J. 2006;25:1046-57 pubmed
    ..These results identify a new level of control on E2F activity and, at a more general level, suggest that 14-3-3 proteins integrate E2F activity with the DNA damage response. ..
  13. Yamada M, Kondo T, Ashizawa S, Takebayashi T, Higashi H, Hatakeyama M. Role of pRB-family/E2F complex in the inhibition of IL-3-dependent lymphoid cell proliferation. Cytokine. 2002;17:91-7 pubmed
    ..Our results indicate that blocking E2F-dependent transactivation, but not the formation of p130-E2F transcriptional repressor complexes, is responsible for the inhibition of IL-3-dependent cell growth by p130. ..
  14. Montigiani S, Muller R, Kontermann R. Inhibition of cell proliferation and induction of apoptosis by novel tetravalent peptides inhibiting DNA binding of E2F. Oncogene. 2003;22:4943-52 pubmed
    ..These results provide new insights into the function of E2F and further validate E2F as a potential therapeutic target in proliferative diseases. ..
  15. Angelis E, Garcia A, Chan S, Schenke Layland K, Ren S, Goodfellow S, et al. A cyclin D2-Rb pathway regulates cardiac myocyte size and RNA polymerase III after biomechanical stress in adult myocardium. Circ Res. 2008;102:1222-9 pubmed publisher
  16. Geiser V, Jones C. Stimulation of bovine herpesvirus-1 productive infection by the adenovirus E1A gene and a cell cycle regulatory gene, E2F-4. J Gen Virol. 2003;84:929-38 pubmed
    ..E2F-1 and E2F-2 strongly activate the IEtu1 promoter, but not a BHV-1 IEtu2 promoter or a herpes simplex virus type 1 ICP0 promoter construct. These studies suggest that E2F family members can stimulate BHV-1 productive infection. ..
  17. Yang Q, Hu J, Ye D, Zhao C, Song S, Gong W, et al. Identification and expression analysis of two zebrafish E2F5 genes during oogenesis and development. Mol Biol Rep. 2010;37:1773-80 pubmed publisher
    ..Interestingly, zE2F5b mRNA is detected later in the lens and optic tectum while zE2F5a mRNA is absent. Our data suggests that E2F5 may play important roles in zebrafish brain, eye and ovarian development. ..
  18. Wan Z, Zhi N, Wong S, Keyvanfar K, Liu D, Raghavachari N, et al. Human parvovirus B19 causes cell cycle arrest of human erythroid progenitors via deregulation of the E2F family of transcription factors. J Clin Invest. 2010;120:3530-44 pubmed publisher
    ..These findings provide new insight into the molecular pathogenesis of B19V in highly permissive erythroid progenitors...
  19. Ruckert F, Joensson P, Saeger H, Grutzmann R, Pilarsky C. Functional analysis of LOXL2 in pancreatic carcinoma. Int J Colorectal Dis. 2010;25:303-11 pubmed publisher
    ..Our results suggest that the improved response toward chemotherapy in LOLX2-silenced pancreatic cancer cells is possibly mediated by the transcription factor E2F5. ..
  20. Halaban R, Cheng E, Smicun Y, Germino J. Deregulated E2F transcriptional activity in autonomously growing melanoma cells. J Exp Med. 2000;191:1005-16 pubmed
  21. Tyagi A, Agarwal C, Agarwal R. The cancer preventive flavonoid silibinin causes hypophosphorylation of Rb/p107 and Rb2/p130 via modulation of cell cycle regulators in human prostate carcinoma DU145 cells. Cell Cycle. 2002;1:137-42 pubmed
    ..Together, these results suggest that silibinin caused hypophosphorylation of Rb-related proteins may in part be responsible for its cancer preventive and anti-carcinogenic efficacy in different cancer models including PCA. ..
  22. Dar A, Majid S, De Semir D, Nosrati M, Bezrookove V, Kashani Sabet M. miRNA-205 suppresses melanoma cell proliferation and induces senescence via regulation of E2F1 protein. J Biol Chem. 2011;286:16606-14 pubmed publisher
    ..E2F1 overexpression in miR-205-expressing cells partially reversed the effects on melanoma cell growth and senescence. These results demonstrate a novel role for miR-205 as a tumor suppressor in melanoma. ..
  23. Kusek J, Greene R, Nugent P, Pisano M. Expression of the E2F family of transcription factors during murine development. Int J Dev Biol. 2000;44:267-77 pubmed
  24. Morris L, Allen K, La Thangue N. Regulation of E2F transcription by cyclin E-Cdk2 kinase mediated through p300/CBP co-activators. Nat Cell Biol. 2000;2:232-9 pubmed
    ..These results indicate that E2F activity may be directly regulated by cyclin E-Cdk2, and imply an autoregulatory mechanism for cell-cycle-dependent transcription through the CDK-stimulated interaction of E2F with p300/CBP co-activators. ..
  25. Donzelli S, Fontemaggi G, Fazi F, Di Agostino S, Padula F, Biagioni F, et al. MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function. Cell Death Differ. 2012;19:1038-48 pubmed publisher
    ..p21(waf1) protein localizes to the cytoplasmic compartment, where it exerts an anti-apoptotic effect by preventing pro-caspase-3 cleavage. This study emphasizes miRNA-128-2 role as a master regulator in NSCLC chemoresistance. ..
  26. Ebelt H, Hufnagel N, Neuhaus P, Neuhaus H, Gajawada P, Simm A, et al. Divergent siblings: E2F2 and E2F4 but not E2F1 and E2F3 induce DNA synthesis in cardiomyocytes without activation of apoptosis. Circ Res. 2005;96:509-17 pubmed
    ..Our finding that expression of E2F2 induces cell division of cardiomyocytes along with a suppression of proapoptotic genes might open a new access to improve the regenerative capacity of cardiomyocytes. ..
  27. Chang W, Andrews J, Carter D, Dagnino L. Differentiation and injury-repair signals modulate the interaction of E2F and pRB proteins with novel target genes in keratinocytes. Cell Cycle. 2006;5:1872-9 pubmed
    ..Thus, multiple combinations of E2F and pRb family proteins may associate with and transcriptionally regulate a given target promoter in response to differentiation and injury-repair stimuli in epidermal keratinocytes. ..
  28. Vaishnav Y, Vaishnav M, Pant V. The molecular and functional characterization of E2F-5 transcription factor. Biochem Biophys Res Commun. 1998;242:586-92 pubmed
    ..We have also demonstrated the presence of a strong transactivation domain at the carboxy terminus (273-346 amino acid residues) of E2F-5 protein. ..
  29. Macaluso M, Montanari M, Marshall C, Gambone A, Tosi G, Giordano A, et al. Cytoplasmic and nuclear interaction between Rb family proteins and PAI-2: a physiological crosstalk in human corneal and conjunctival epithelial cells. Cell Death Differ. 2006;13:1515-22 pubmed
  30. Collins Y, Tan D, Pejovic T, Mor G, Qian F, Rutherford T, et al. Identification of differentially expressed genes in clinically distinct groups of serous ovarian carcinomas using cDNA microarray. Int J Mol Med. 2004;14:43-53 pubmed
    ..Our study demonstrates differential gene expression in clinically distinct groups of SEOC using cDNA microarray. These genes may potentially be useful as biomarkers and/or targets for therapeutic intervention. ..
  31. Zhao J, Wu X, Ling X, Lin Z, Fu X, Deng Y, et al. Analysis of genetic aberrations on chromosomal region 8q21-24 identifies E2F5 as an oncogene with copy number gain in prostate cancer. Med Oncol. 2013;30:465 pubmed publisher
    ..5, P ? 0.001). Our data offers the convincing evidence that the copy number gains of E2F5 and MYC may play an important role in genesis and progression of PCa. Especially, E2F5 may be a novel potential candidate marker for malignant PCa. ..
  32. Scime A, Li L, Ciavarra G, Whyte P. Cyclin D1/cdk4 can interact with E2F4/DP1 and disrupts its DNA-binding capacity. J Cell Physiol. 2008;214:568-81 pubmed
    ..These data support a model in which E2F4 DNA binding is abolished during mid-G(1) at the same time when E2F interactions with pRb-related proteins are disrupted by cyclin D1/cdk4. ..
  33. Buck V, Allen K, Sørensen T, Bybee A, Hijmans E, Voorhoeve P, et al. Molecular and functional characterisation of E2F-5, a new member of the E2F family. Oncogene. 1995;11:31-8 pubmed
    ..The structural and functional similarity of E2F-5 and E2F-4 defines a subfamily of E2F proteins. ..
  34. Magae J, Illenye S, Chang Y, Mitsui Y, Heintz N. Association with E2F-1 governs intracellular trafficking and polyubiquitination of DP-1. Oncogene. 1999;18:593-605 pubmed
    ..Our studies indicate association with E2F subunits prevents ubiquitin-dependent degradation of DP-1 in the cytoplasm by promoting nuclear entry of E2F/DP heterodimers. ..
  35. D Souza S, Pajak A, Balazsi K, Dagnino L. Ca2+ and BMP-6 signaling regulate E2F during epidermal keratinocyte differentiation. J Biol Chem. 2001;276:23531-8 pubmed
    ..p130.HDAC1 complexes are likely involved in the permanent withdrawal from the cell cycle of keratinocytes responding to differentiation stimuli. ..
  36. Itoh A, Levinson S, Morita T, Kourembanas S, Brody J, Mitsialis S. Structural characterization and specificity of expression of E2F-5: a new member of the E2F family of transcription factors. Cell Mol Biol Res. 1995;41:147-54 pubmed
    ..The structural divergence between the two branches of the E2F family may thus reflect participation in different regulatory networks. ..
  37. Kothandaraman N, Bajic V, Brendan P, Huak C, Keow P, Razvi K, et al. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer. BMC Cancer. 2010;10:64 pubmed publisher
    ..approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease...
  38. 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. ..
  39. Satoh T, Toyoda M, Hoshino H, Monden T, Yamada M, Shimizu H, et al. Activation of peroxisome proliferator-activated receptor-gamma stimulates the growth arrest and DNA-damage inducible 153 gene in non-small cell lung carcinoma cells. Oncogene. 2002;21:2171-80 pubmed
    ..These findings collectively indicated that activation of PPAR-gamma by TZDs could cause growth inhibition and apoptosis of NSCLC cells and that GADD153 might be a candidate factor implicated in these processes. ..
  40. Fujita N, Furukawa Y, Itabashi N, Okada K, Saito T, Ishibashi S. Differences in E2F subunit expression in quiescent and proliferating vascular smooth muscle cells. Am J Physiol Heart Circ Physiol. 2002;283:H204-12 pubmed
    ..In contrast, both FBS and vasoconstrictive hormones drove transcription of the cdc6 gene by downregulating p130 and recruiting free E2F-3 in the latter, which underlies the progression of VSMC into S phase. ..
  41. Umemura S, Shirane M, Takekoshi S, Kusakabe T, Itoh J, Egashira N, et al. Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome. Br J Cancer. 2009;100:764-71 pubmed publisher
    ..This E2F-5-positive breast cancer subtype was associated with an ER(-)/PgR(-)/HER2(-) status, a basal phenotype, and a worse clinical outcome. ..
  42. Yoshida K, Inoue I. Regulation of Geminin and Cdt1 expression by E2F transcription factors. Oncogene. 2004;23:3802-12 pubmed
  43. 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. ..
  44. Caracciolo V, Reiss K, Crozier Fitzgerald C, De Pascali F, Macaluso M, Khalili K, et al. Interplay between the retinoblastoma related pRb2/p130 and E2F-4 and -5 in relation to JCV-TAg. J Cell Physiol. 2007;212:96-104 pubmed
    ..Moreover, Small interference RNA experiments directed toward silencing the Rb2/p130 gene demonstrated that pRb2/p130 does not play a predominant role in the nuclear transportation of E2F4 and E2F5. ..
  45. Reed S, Ouellette S, Liu X, Allen R, Johnson S. E2F5 and LEK1 translocation to the nucleus is an early event demarcating myoblast quiescence. J Cell Biochem. 2007;101:1394-408 pubmed
    ..Our results indicate that Raf-arrested myoblasts may serve as a model system for satellite cell cycle studies and that E2F5 and LEK1 translocation to the nucleus is an important first step during entry into quiescence. ..
  46. Ohtani N, Brennan P, Gaubatz S, Sanij E, Hertzog P, Wolvetang E, et al. Epstein-Barr virus LMP1 blocks p16INK4a-RB pathway by promoting nuclear export of E2F4/5. J Cell Biol. 2003;162:173-83 pubmed
    ..These results reveal a novel activity of LMP1 and increase an understanding of how viral oncoproteins perturb the p16INK4a-RB pathway. ..
  47. Swetloff A, Ferretti P. Changes in E2F5 intracellular localization in mouse and human choroid plexus epithelium with development. Int J Dev Biol. 2005;49:859-65 pubmed
  48. Teissier S, Pang C, Thierry F. The E2F5 repressor is an activator of E6/E7 transcription and of the S-phase entry in HPV18-associated cells. Oncogene. 2010;29:5061-70 pubmed publisher
    ..Diverting the function of E2F5 from a cell-cycle repressor into an activator might contribute to the higher oncogenic potential of HPV18 when compared with other high-risk HPV types...
  49. Jiang Y, Yim S, Xu H, Jung S, Yang S, Hu H, et al. A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma. World J Gastroenterol. 2011;17:470-7 pubmed publisher
    ..021). To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells. ..
  50. Kolupaeva V, Basilico C. Overexpression of cyclin E/CDK2 complexes overcomes FGF-induced cell cycle arrest in the presence of hypophosphorylated Rb proteins. Cell Cycle. 2012;11:2557-66 pubmed publisher
    ..Our data also highlight the importance of E2F4/p130 complexes for FGF-mediated growth arrest in chondrocytes. ..
  51. Vaishnav Y, Pant V. Differential regulation of E2F transcription factors by p53 tumor suppressor protein. DNA Cell Biol. 1999;18:911-22 pubmed
    ..The complex interplay between various positive and negative regulators of cell growth, such as E2F and p53 proteins, may be crucial in determining the ultimate outcome in terms of cell cycle arrest, cell growth, or apoptosis. ..
  52. Arbi M, Pefani D, Kyrousi C, Lalioti M, Kalogeropoulou A, Papanastasiou A, et al. GemC1 controls multiciliogenesis in the airway epithelium. EMBO Rep. 2016;17:400-13 pubmed publisher
    ..GemC1-knockout mice are born with airway epithelia devoid of multiciliated cells. Our results identify GemC1 as an essential regulator of ciliogenesis in the airway epithelium and a candidate gene for mucociliary disorders. ..
  53. Cai C, Huo Q, Wang X, Chen B, Yang Q. SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5. Biochem Biophys Res Commun. 2017;485:272-278 pubmed publisher
    ..Taken together, our findings indicated that SNHG16 induces breast cancer cell migration by competitively binding miR-98 with E2F5, and SNHG16 can serve as a potential therapeutic target for breast cancer treatment. ..