Skip to main content
SpringerLink
Log in

Function of the E2F Transcription Factor Family During Normal and Pathological Growth

  • Chapter
Transcription Factors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 166))

  • 441 Accesses

Abstract

The E2F family of transcription factors elicits opposing roles in transcriptional activation and repression during the regulation of proliferation, apoptosis, and DNA repair and thus contributes to tumor suppression, oncogenesis, and differentiation. A vast array of studies have confirmed that the intracellular pathway controlling the activity of E2F and its main regulato r, the retinoblastoma tumor suppressor protein (pRb) is disrupted in virtually all human cancers. Based on their ability to promote either proliferation or cell cycle withdrawal and differentiation, the individual E2Fs can be subdivided into three different groups. In this review, we focus on the relative contribution of two distinct E2F subclasses to gene activation and repression. However, critical questions remain to be answered as to the specific role played by individual E2Fs in growth control and whether the current concepts of E2F/pRb action explain all of the functions of these proteins in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Adams M, Sears R, Nuckolls F, Leone G, Nevins JR (2000) Complex transcriptional regulatory mechanism control expression of the E2F3 locus. Mol Cell Biol 20:3633–3639

    Article  PubMed  CAS  Google Scholar 

  • Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL, Vousden KH (1998) p14ARF links the tumour suppressors RB and p53. Nature 395:124–125

    Article  PubMed  CAS  Google Scholar 

  • Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T (1998) Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391:597–601

    Article  PubMed  CAS  Google Scholar 

  • Bruce JL, Hurford RK, Classon M, Koh J, Dyson N (2000) Requirements for cell cycle arrest by p16INK4 Mol Cell 6:737–742

    Article  PubMed  CAS  Google Scholar 

  • Cartwright P, Müller H, Wagener C, Holm K, Helin K (1998) E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription. Oncogene 17:611–623

    Article  PubMed  CAS  Google Scholar 

  • Chen CR, Kang Y, Siegel PM, Massague J (2002) E2F4/5 and pl07 as Smad cofactors linking the TGF-receptor to c-myc repression. Cell 110:19–32

    Article  PubMed  CAS  Google Scholar 

  • Classon M, Salama S, Gorka C, Mulloy R, Braun P, Harlow E (2000) Combinatorial roles for pRB, p107, and p130 in E2F-mediated cell cycle control. Proc Natl Acad Sci USA 97:10820–10825

    Article  PubMed  CAS  Google Scholar 

  • Cloud JE, Rogers C, Reza TL, Ziebold U, Stone JR, Picard MH, Caron AM, Bronson RT, Lees JA (2002) Mutant mouse models reveal the relative roles of E2F1 and E2F3 in vivo. Mol Cell Biol 22:2663–2672

    Article  PubMed  CAS  Google Scholar 

  • Cobrinik D, Lee MH, Hannon G, Mulligan G, Bronson RT, Dyson N, Harlow E, Beach D, Weinberg RA, Jacks T (1996) Shared role of the pRb-related p130 and p107 proteins in limb development. Genes Dev 10:1633–1644

    Article  PubMed  CAS  Google Scholar 

  • Cook WD, McCaw BJ (2000) Accommodating haploinsufficient tumour suppressor genes in Knudsońs model. Oncogene 19:3434–3438

    Article  PubMed  CAS  Google Scholar 

  • Dannenberg JH, van Rossum A, Schuijff L, te Riele H (2000) Ablation of the retinoblastoma gene family deregulates GI control causing immortilization and increased cell turnover under growth-restricting conditions. Genes Dev 14:3051–3064

    Article  PubMed  CAS  Google Scholar 

  • De Bruin A, Maiti B, Jakoi L, Timmers C, Leone G (2003) Identification and characterization of E2F7, a novel mammalian E2F family member capable of blocking cellular proliferation. J Biol Chem 278:42041–42049

    Article  PubMed  Google Scholar 

  • DeGregori J, Kowalik T, Nevins JR (1995a) Cellular targets for activation by the E2F1 transcripion factor include DNA synthesis-and G1/S-regulatory genes. Mol Cell Biol 15:4215–4224

    PubMed  CAS  Google Scholar 

  • DeGregori J, Leone G, Ohtani K, Miron A, Nevins JR (1995b) E2F-1 accumulation bypasses a G1 arrest resulting from the inhibition of G1 cyclin-dependent kinase activity. Genes Dev 9:2873–2887

    Article  PubMed  CAS  Google Scholar 

  • De la Luna S, Burden MJ, Lee CW, Thangue NB (1996) Nuclear accumulation of the E2F heterodimer regulated by subunit composition and alternative splicing of a nuclear localization signal. J Cell Sci 109:2443–2452

    PubMed  Google Scholar 

  • Fagan R, Flint KJ, Jones N (1994) Phosphorylation of E2F-1 modulates its interaction with the retinoblastoma gene product and the adenoviral E4 19 kDa protein. Cell 78:799–811

    Article  PubMed  CAS  Google Scholar 

  • Field SJ, Tsai FY, Kuo F, Zubiaga AM, Kaelin WG, Livingston DM, Orkin SH, Greenberg ME (1996) E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell 85:549–561

    Article  PubMed  CAS  Google Scholar 

  • Frolov MV, Huen DS, Stevaux O, Dessislava D, Balsczarek-Strang K, Elsdon M, Dyson NJ (2001) Functional antagonism between E2F family members. Genes Dev 15:2146–2160

    Article  PubMed  CAS  Google Scholar 

  • Gaubatz S, Lees JA, Lindeman GJ, Livingston DM (2001) E2F4 is exported from the nucleus in a CRM1-dependent manner. Mol Cell Biol 21:1384–1392

    Article  PubMed  CAS  Google Scholar 

  • Gaubatz S, Lindemann GJ, Ishida S, Jakoi L, Nevins JR, Livingston DM, Rempel RE (2000) E2F4 and E2F5 play an essential role in pocket protein-mediated G1 control. Mol Cell 6:729–735

    Article  PubMed  CAS  Google Scholar 

  • Gaubatz S, Wood JG, Livingston DM (1998) Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6. PROC NATL ACAD SCI USA 95:9190–9195

    Article  PubMed  CAS  Google Scholar 

  • Gosh MK, Harter ML (2003) Aviral mechanism for remodeling chromatin structure in G0 cells. Mol Cell 12:255–260

    Article  Google Scholar 

  • He Y, Armanious MK, Thomas MJ, Cress WD (2000) Identificaton of E2F3B, an alternative from of E2F-3 lacking a conserved N-terminal region. Oncogene 19:3422–3433

    Article  PubMed  CAS  Google Scholar 

  • Helin K, Wu CL, Fattaey AR, Lees JA, Dynlacht BD, Ngwu C, Harlow E (1993) Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation. Genes Dev 7:1850–1861

    Article  PubMed  CAS  Google Scholar 

  • Helt AM, Galloway DA (2003) Mechanisms by which DNA tumor virus oncoproteins target the Rb family of pocket proteins. Carcinogenesis 24:159–169

    Article  PubMed  CAS  Google Scholar 

  • Hsieh JK, Fredersdorf S, Kouzarides T, Martin K, Lu X (1997) E2F1-induced apoptosis requires DNA binding but not transactivation and is inhibited by the retinoblastoma protein through direct interaction. Genes Dev 11:1840–1852

    Article  PubMed  CAS  Google Scholar 

  • Humbert PO, Rogers C, Ganiatsas S, Landsberg RL, Trimarchi JM, Dandapani S, Brugnara C, Erdman S, Schrenzel M, Bronson R, Lees JA (2000a) E2F4 is essential for normal erythrocyte maturation and neonatal viability. Mol Cell 6:281–291

    Article  PubMed  CAS  Google Scholar 

  • Humbert PO, Verona R, Trimarchi JM, Rogers C, Dandapani S, Lees JA (2000b) E2f3 is critical for normal cellular proliferation. Genes Dev 14:690–703

    PubMed  CAS  Google Scholar 

  • Hurford RK, Cobrinik D, Lee MH, Dyson N (1997) pRb and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes Dev 11:1447–1463

    Article  PubMed  CAS  Google Scholar 

  • Ikeda MA, Lakoi L, Nevins JR (1996) A unique role for the Rb protein in controlling E2F accumulation during cell growth and differentiation. Proc Natl Acad Sci USA 93:3215–3220

    Article  PubMed  CAS  Google Scholar 

  • Ishida S, Huang E, Zuzan H, Spang R, Leone G, West M, Nevins JR (2001) Role for E2F in control of both DNA replication and mitotic functions as revealed from DNA microarray analysis. Mol Cell Biol 21:4684–4699

    Article  PubMed  CAS  Google Scholar 

  • Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA (1992) Effects of an Rb mutation in the mouse. Nature 359:295–300

    Article  PubMed  CAS  Google Scholar 

  • Johnson DG, Ohtani K, Nevins JR (1994) Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. Genes Dev 8:1514–1525

    Article  PubMed  CAS  Google Scholar 

  • Knudsen ES, Buckmaster C, Chen TT, Feramisco JR, Wang JYJ (1998) Inhibition of DNA synthesis by RB: effects on G1/S transition and S-phase progression. Genes Dev 12:2278–2292

    Article  PubMed  CAS  Google Scholar 

  • Lasorella A, Noseda M, Beyna M, Iavarone A (2000) Id2 is a retinoblastoma protein target that mediates signalling by myc. Nature 407:592–598

    Article  PubMed  CAS  Google Scholar 

  • LeCouter JE, Kablar B, Whyte PFM, Ying C, Rudnicki M (1998) Strain-dependent embryonic lethality in mice lacking the retinoblastoma-related p130 gene. Development 125:4669–4679

    PubMed  CAS  Google Scholar 

  • Lee EY, Cam H, Ziebold U, Rayman JB, Lees JA (2002) E2F4 loss suppresses tumorigenesis in Rb mutant mice. Cancer Cell 2:463–472

    Article  PubMed  CAS  Google Scholar 

  • Lee MH, Williams BO, Mulligan G, Mukai S, Bronson RT, Dyson N, Harlow E, Jacks T (1996) Targeted disruption of p107: functional overlap between p107 and pRb. Genes Dev 10:1621–1632

    Article  PubMed  CAS  Google Scholar 

  • Leone G, Sears R, Huang E, Rempel R, Nuckolls F, Park CH, Giangrande P, Wu L, Saavedra HI, Field SJ, Thompson MA, Yang H, Fujiwara Y, Greenberg ME, Orkin S, Smith C, Nevins JR (2001) Myc requires distinct E2F activities to induce S phase and apoptosis. Mol Cell 8:105–113

    Article  PubMed  CAS  Google Scholar 

  • Leone G, Nuckolls F, Ishida S, Adams M, Sears R, Iakoi L, Miron A, Nevins JR (2000) Identification of a novel E2F3 product suggests a mechanism for determining specificity of repression by Rb proteins. Mol Cell Biol 20:3626–3632

    Article  PubMed  CAS  Google Scholar 

  • Leone G, DeGregori J, Yan Z, Jakoi L, Ishida S, Williams RS, Nevins JR (1998) E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes Dev 12:2120–2130

    Article  PubMed  CAS  Google Scholar 

  • Li FX, Zhu JW, Hogan Cl, DeGregori J (2003) Defective gene expression; S phase progression, and Maturation during hematopoiesis in E2F1/E2F2 mutant mice. Mol Cell Biol 23:3607–3622.

    Article  PubMed  CAS  Google Scholar 

  • Lindemann GJ, Dagnino L, Gaubatz S, Xu Y, Bronson RT, Warren HB, Livingston DM (1998) A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting. Genes Dev 12:1092–1098

    Article  Google Scholar 

  • Lindeman GJ, Gaubatz S, Livingston DM, Ginsberg D (1997) The subcellular localization of E2F-4 is cell-cycle dependent. Proc Natl Acad Sci USA 94:5095–5100

    Article  PubMed  CAS  Google Scholar 

  • Lomazzi M, Moronie MC, Jensen MR, Frittoli E, Helin K (2002) Suppression of the p53or pRb-mediated G1 checkpoint is required for E2F-induced S-phase entry. Nat Genet 31:190–194

    Article  PubMed  CAS  Google Scholar 

  • Lukas J, Herzinger T, Hansen K, Moroni MC, Resnitzky D, Helin K, Reed SI, Bartek J (1997) Cyclin E-induced S phase without activation of th pRb/E2F pathway. Genes Dev 11:1479–1492

    Article  PubMed  CAS  Google Scholar 

  • Lukas J, Peterson BO, Holm K, Bartek J, Helin K (1996) Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4-mediated growth suppression. Mol Cell Biol 16:1047–1057

    PubMed  CAS  Google Scholar 

  • Lukas J, Bartkova J, Rohde M, Strauss M, Bartek J (1995) Cyclin D1 is dispensable for G1 control in retinoblastoma gene-deficient cells independently of cdk4 activity. Mol Cell Biol 15:2600–2611

    PubMed  CAS  Google Scholar 

  • Magae J, Wu CL, Illenye S, Harlow E, Heintz NH (1996) Nuclear localization of DP and E2F transcription factors by heterodimeric partners and retinoblastoma protein family members. J Cell Sci 109:1717–1726

    PubMed  CAS  Google Scholar 

  • Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain IP, Troalen F, Trouche D, Harel-Bellan A (1998) Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature 391:601–604

    Article  PubMed  CAS  Google Scholar 

  • Martin K, Trouche D, Hagemeier C, Sorenson TS, La Thangue NB, Kouzarides T (1995) Stimulation of E2F1/DP1 transcriptional activity by MDM 2 oncoprotein. Nature 375:691–694

    Article  PubMed  CAS  Google Scholar 

  • Medema RH, Herrera RE, Lam F, Weinberg RA (1995) Growth suppression by p16INK4 requires functional retinoblastoma protein. Proc Natl Acad Sci USA 92:6289–6293

    Article  PubMed  CAS  Google Scholar 

  • Moberg K, Starz MA, Lees JA (1996) E2F-4 switches from p130 to p107 and pRb in response to cell cycle reentry. Mol Cell Biol 16:1436–1449

    PubMed  CAS  Google Scholar 

  • Morkel M, Wenkel J, Bannister AJ, Kouzarides T, Hagemeier C (1997) An E2F-like repressor of transcription. Nature 390:567–568

    Article  PubMed  CAS  Google Scholar 

  • Moroni MC, Hickman ES, Denchi EL, Caprara G, Colli E, Cecconi F, Müller H, Helin K (2001) Apaf-1 is a transcriptional targ et for E2F and p53. Nat Cell Biol 3:552–558

    Article  PubMed  CAS  Google Scholar 

  • Müller H, Bracken AP, Vernell R, Moroni MC, Christians F, Grassilli E, Prosperini E, Vigo E, Oliner JD, Helin K (2001) E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. Genes Dev 15:267–285

    Article  PubMed  Google Scholar 

  • Müller H, Moroni MC, Vigo E, Peterson BO, Bartek J, Helin K (1997) Induction of S-phase entry by E2F transcription factors depends on their nuclear localization. Mol Cell Biol 17:5508–5520

    PubMed  Google Scholar 

  • Nahle Z, Polakoff J, Davuluri RV, McCurrach ME, Jacobson MD, Narita M, Zhang MQ, Lazebnik Y, Bar Sagi D, Lowe SW (2002) Direct coupling of the cell cycle and cell death machinery by E2F. Nat Cell Biol 4:859–864

    Article  PubMed  CAS  Google Scholar 

  • Narita M, Nun S, Heard E, Narita M, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113:703–716

    Article  PubMed  CAS  Google Scholar 

  • Ogawa H, Ishiguro KI, Gaubatz S, Livingston DM, Nakatani Y (2002) A complex with chromatin modifiers that occupies E2F-and myc-responsive genes in G0 cell. Science 296:1132–1136

    Article  PubMed  CAS  Google Scholar 

  • Pan H, Yin C, Dyson NJ, Harlow E, Yamasaki L, Van Dyke T (1998) Key roles for E2F1 in signaling p53-dependent apoptosis and in cell division within developing tumors. Mol Cell 2:283–292

    Article  PubMed  CAS  Google Scholar 

  • Phillips CP, Ernst MK, Bates S, Rice NR, Vousden KH (1999) E2F-1 potentiates cell death by blocking antiapoptotic signalling pathways. Mol Cell 4:771–781

    Article  PubMed  CAS  Google Scholar 

  • Phillips AC, Bates S, Ryan KM, Helin K, Vousden KH (1997) Induction of DNA synthesis and apoptosis are separable functions of E2F-1. Genes Dev 11:1853–1863

    Article  PubMed  CAS  Google Scholar 

  • Rayman JB, Takahashi Y, Indjeian VB, Dannenberg JH, Catchpole S, Watson RJ, te Riele H, Dynlacht, BD (2002) E2F mediates cell cycle-dependent transcriptional repression in vivo by recruitment of an HDAC1/mSin3B corepressor complex. Genes Dev 16:933–947

    Article  PubMed  CAS  Google Scholar 

  • Rempel RE, Saenz-Robles MT, Storms R, Morham S, Ishida S, Engel A, Jakoi L, Melhem MF, Pipas JM, Smith C, Nevins JR (2000) Loss of E2F4 activity leads to abnormal development of multiple cellular lineages. Mol Cell 6:293–306

    Article  PubMed  CAS  Google Scholar 

  • Ren B, Cam H, Takahashi Y, Volkert T, Terragni J, Young RA, Dynlacht BD (2002) E2F integrates cell cycle progression with DNA repair, replication, and G2/M checkpoints. Genes Dev 16:245–256

    Article  PubMed  CAS  Google Scholar 

  • Ross JF, Näär A, Cam H, Gregory R, Dynlacht BD (2001) Active repression and E2F inhibition by pRB are biochemically distinguishable. Genes Dev 15:392–397

    Article  PubMed  CAS  Google Scholar 

  • Ross JF, Liu X, Dynlacht BD (1999) Mechanism of transcriptional repression of E2F by the retinoblastoma tumor suppressor protein. Mol Cell 3:195–205

    Article  PubMed  CAS  Google Scholar 

  • Rowland BD, Denissov SG, Douma S, Stunnenberg HG, Bernards R, Peeper DS (2002) E2F transcriptional repressor complexes are critical downstream targets of p19ARF/p53-induced proliferative arrest. Cancer Cell 2:55–65

    Article  PubMed  CAS  Google Scholar 

  • Saavedra HI, Maiti B, Timmers C, Altura R, Tokuyama Y, Fukasawa K, Leone G (2003) Inactivation of E2F3 results in centrosome amplification. Cancer Cell 3:333–346

    Article  PubMed  CAS  Google Scholar 

  • Sage J, Mulligan GJ, Attardi LD, Miller A, Chen SQ, Williams B, Theodorou E, Jacks T (2000) Targeted disruption of the three Rb-related genes leads to loss of G1 control and immortalization. Genes Dev 14:3037–3050

    Article  PubMed  CAS  Google Scholar 

  • Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chien A, Weinberg RA (1995) 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 USA 92:2403–2407

    Article  PubMed  CAS  Google Scholar 

  • Sears, R, Ohtani K, Nevins JR (1997) Identifiction of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals. Mol Cell Biol 17:5227–5235

    PubMed  CAS  Google Scholar 

  • Sellers WR, Novitch BG, Miyake S, Heith A, Otterson GA, Kaye FJ, Lassar AB, Kaelin WG (1998) Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth. Genes Dev 12:95–106

    Article  PubMed  CAS  Google Scholar 

  • Shan B, Durfee T, Lee WH (1996) Disruption of RB/E2F-1 interaction by single point mutations in E2F-1 enhances S-phase entry and apoptosis. Proc Natl Acad Sci USA 93:679–684

    Article  PubMed  CAS  Google Scholar 

  • Shan B, Chang CY, Jones D, Lee WH (1994) The transcription factors E2F-1 mediates the autoregulation of RB gene expression. Mol Cell Biol 14:299–309

    PubMed  CAS  Google Scholar 

  • Sherr CJ, Roberts JM (I999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13:1501–1512

    Article  Google Scholar 

  • Smith EJ, Leone G, Nevins JR (1998) Distinct mechanisms control the accumulation of the Rb-related p107 and p130 proteins during cell growth. Cell Growth Diff 9:297–303

    PubMed  CAS  Google Scholar 

  • Smith EJ, Leone G, DeGregori J, Jakoi L, Nevins JR (1996) The accumulation of an E2F-p130 transcriptional repressor distinguishes a G0 cell state from a G1 cell state. Mol Cell Biol 16:6965–6976

    PubMed  CAS  Google Scholar 

  • Stiewe T, Pützer BM (2000) Role of the p53-homologue p73 in E2F1-induced apoptosis. Nat Genet 26:464–469

    Article  PubMed  CAS  Google Scholar 

  • Storre J, Elsässer HP, Fuchs M, Ullmann D, Livingston DM, Gaubatz S (2002) Homeotic transformations of the axial skeleton that accompany a targeted deletion of E2f6. EMBO J 3:695–700

    Article  CAS  Google Scholar 

  • Takahashi Y, Rayman JB, Dynlacht BD (2000) Analysis of promoter binding by the E2F and pRb families in vivo: distinct E2F proteins mediate activation and repression. Trimarchi JM, Lees JA (2001) Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 3:11–20

    Google Scholar 

  • Tsai KY, Hu Y, Macleod KF, Crowley D, Yamasaki L, Jacks T (1998) Mutation of E2F-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol Cell 2:293–304

    Article  PubMed  CAS  Google Scholar 

  • Verona R, Moberg K, Estes S, Starz M, Vernon JP, Lees JA (1997) E2F activity is regulated by cell cycle-dependent changs in subcellular localization. Mol Cell Biol 17:7268–7282

    PubMed  CAS  Google Scholar 

  • Wang D, Russel JL, Johnson (2000) E2F4 and E2F1 have similar proliferative properties but different apoptotic and oncogenic properties in vivo. Mol Cell Biol 20:3417–3424

    Article  PubMed  CAS  Google Scholar 

  • Wang ZM, Yang H, Livingston D (1998) Endogenous E2F-1 promotes timely G0 exit of resting mouse embryo fibroblasts. Proc Natl Acad Sci USA 95:15583–15586

    Article  PubMed  CAS  Google Scholar 

  • Weinmann AS, Yan PS, Oberley MJ, Huang THM, Farnham PJ (2002) Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis. Genes Dev 16:235–244

    Article  PubMed  CAS  Google Scholar 

  • Wells J, Boyd KE, Fry C, Bartley SM, Farnham PJ (2000) Target gene specificity of E2F and pocket protein family members in living cells. Mol Cell Biol 20:5797–5807

    Article  PubMed  CAS  Google Scholar 

  • Wu CH, Classon M, Dyson N, Harlow E (1996) Exprssion of dominant-negative mutant DP-l blocks cell cycle progression in GI. Mol Cell Biol 16:3698–3706

    PubMed  CAS  Google Scholar 

  • Wu L, de Bruin A, Saavedra HI, Starovic M, Trimboli A, Yang Y, Ostrowski MC, Rosol TJ, Woollett LA, Weinstein M, Cross JC, Robinson ML, Leone G (2003) Extra-embryonic function of Rb is essential for embryonic development and viability. Nature 421:942–947

    Article  PubMed  CAS  Google Scholar 

  • Wu L, Timmers C, Maiti B, Saavedra HI, Sang L, Chong GT, Nuckolls F, Giangrande P, Wright FA, Field SJ, Greenberg ME, Orkin S, Nevins JR, Robinson ML, Leone G (2001) The E2FI-3 transcription factors are essential for cellular proliferation. Nature 414:457–462

    Article  PubMed  CAS  Google Scholar 

  • Yamasaki L, Jacks T, Bronson R, Goillot E, Harlow E, Dyson NJ (1996) Tumor induction and tissue atrophy in mice laking E2F-1. Cell 85:537–548

    Article  PubMed  CAS  Google Scholar 

  • Zhang HS, Gavin M, Dahiya A, Postigo AA, Ma D, Luo RX, Harbour JW, Dean DC (2000) Exit from Gland S phase of the cell cycle is regulated by repressor complexes containing HDAC-RB-hSWI/SNF and Rb-hSWI/SNF. Cell 101:79–89

    Article  PubMed  CAS  Google Scholar 

  • Zhang HS, Postigo AA, Dean DC (1999) Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by pI6INK4a, TGFβ, and contact inhibition. Cell 97:53–61

    Article  PubMed  CAS  Google Scholar 

  • Zhu JW, Field SJ, Gore L, Thompson M, Yang H, Fujiwara Y, Cardiff RD, Greenberg M, Orkin SH, DeGregori J (2001) E2F1 and E2F2 determ ine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis. Mol Cell Biol 21:8547–8564

    Article  PubMed  CAS  Google Scholar 

  • Zhu L, Zhu L, Xie E, Chang LS (1995) Differential roles of two tandem E2F sites in repression of the p107 promoter by retinoblastoma and p107 proteins. Mol Cell Biol 15:3552–3562

    PubMed  CAS  Google Scholar 

  • Ziebold U, Lee EY, Bronson RT, Lees JA (2003) E2F3 loss has opposing effects on different pRb-deficient tumors, resulting in suppression of pituitary tumors but metastasis of medullary thyroid carcinomas. Mol Cell Biol 23:6542–6552

    Article  PubMed  CAS  Google Scholar 

  • Ziebold U, Reza T, Caron A, Lees JA (2001) E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Genes Dev 15:386–391

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Klinik mit Schwerpunkt Kardiologie, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    L. Hauck & R. von Harsdorf

Authors
  1. L. Hauck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. von Harsdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. von Harsdorf .

Editor information

Editors and Affiliations

  1. Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13125, Berlin, Germany

    Manfred Gossen

  2. atugen AG, Robert-Rössle-Strasse 10, 13125, Berlin, Germany

    Jörg Kaufmann

  3. Department of Biochemistry and Molecular Biology, Michigan State University, 510 Biochemistry Building, East Lansing, MI, 48824-1319, USA

    Steven J. Triezenberg (Associate Director) (Associate Director)

  4. Graduate Program in Cell and Molecular Biology, Michigan State University, 510 Biochemistry Building, East Lansing, MI, 48824-1319, USA

    Steven J. Triezenberg (Associate Director) (Associate Director)

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag

About this chapter

Cite this chapter

Hauck, L., von Harsdorf, R. (2004). Function of the E2F Transcription Factor Family During Normal and Pathological Growth. In: Gossen, M., Kaufmann, J., Triezenberg, S.J. (eds) Transcription Factors. Handbook of Experimental Pharmacology, vol 166. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18932-6_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-18932-6_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62361-5

  • Online ISBN: 978-3-642-18932-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation