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Growth Regulation by the E2F and DP Transcription Factor Families

  • Chapter
Cell Cycle Control

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 22))

Abstract

What we know about E2F transcriptional activity has been derived from several lines of investigation. Each line of study gives us greater insight into understanding the function of E2F transcriptional activity in growth control. In vivo and in vitro, E2F transcriptional activity appears to be complex, often capable of completely opposing actions. The basis for positive and negative action at many levels appears to be the ability of E2F transcriptional activity to transactivate and repress gene expression, which both require the same initial step, i.e., recognition of target DNA. When bound to the retinoblastoma tumor suppressor (pRB) or other pRB family members, E2F functions as a repressor, and when “free” of pRB family interaction, E2F functions as an activator. It is this positive and negative, up and down nature of E2F activity that fascinates so many investigators.

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References

  • Adams PD, Sellers WR, Sharma SK, Wu AD, Nalin CM, Kaelin WG (1996) Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. Mol. Cell. Biol. 16: 6623–6633.

    PubMed  CAS  Google Scholar 

  • Adnane J, Shao Z, Robbins PD (1995) The retinoblastoma susceptibility gene product represses transcription when directly bound to the promoter. J. Biol. Chem. 270: 8837–8843.

    Article  PubMed  CAS  Google Scholar 

  • Asano M, Nevins JR, Wharton RP (1996) Ectopic E2F expression induces S phase and apoptosis in Drosophila imaginai discs. Genes Dev. 10: 1422–1432.

    Article  PubMed  CAS  Google Scholar 

  • Baldi A, De Luca A, Claudio PP, Baldi F, Giordano GG, Tommasino M, Paggi MG, Giordano A (1995) The Rb2/p130 gene product is a nuclear protein whose phosphorylation is cell cycle regulated. J. Cell. Biochem. 59: 402–408.

    Article  PubMed  CAS  Google Scholar 

  • Bandara LR, Buck VM, Zamanian M, Johnston LH, La Thangue NB (1993) Functional synergy between DP-1 and E2F-1 in the cell cycle-regulating transcription factor DRTF1/E2F. EMBO J. 12: 4317–4324.

    PubMed  CAS  Google Scholar 

  • Bandara LR, Lam EW-R, Sorensen TS, Zamanian M, Girling R, La Thangue NB (1994) DP-1: a cell cycle-regulated and phosphorylated component of transcription factor DRTF1/E2F which is functionally important for recognition by pRB and the adenovirus E4 orf 6/7 protein. EMBO J. 13: 3104–3114.

    PubMed  CAS  Google Scholar 

  • Beijersbergen RL, Carlee L, Kerkhoven RM, Bernards R (1995) Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes. Genes Dev. 9: 1340–1353.

    Article  PubMed  CAS  Google Scholar 

  • Beijersbergen RL, Kerkhoven RM, Zhu L, Carlee L, Voorhoeve PM, Bernards R (1994) E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. Genes Dev. 8: 2680–2690.

    Article  PubMed  CAS  Google Scholar 

  • Birchenall-Roberts MC, Yoo YD, Bertolette IDC, Lee K-H, Turley JM, Bang O-S, Ruscetti FW, Kim S-J (1997) The p120-v-Abl protein interacts with E2F-1 and regulates E2F-1 transcriptional activity. J. Biol. Chem. 272: 8905–8911.

    Article  PubMed  CAS  Google Scholar 

  • Bjorklund S, Hjortsbert K, Johansson E, Thelander L (1993) Structure and promoter characterization of the gene encoding the large subunit (R1 protein) of mouse ribonucleotide reductase. Proc. Natl. Acad. Sci. USA 90: 11322–11326.

    Article  PubMed  CAS  Google Scholar 

  • Blake MC, Azizkhan JC (1989) Transcription factor E2F is required for efficient expression of the hamster dihydrofolate reductase gene in vitro and in vivo. Mol. Cell. Biol. 9: 4994–5002.

    PubMed  CAS  Google Scholar 

  • Botz J, Zerfass-Thome K, Spitkovsky D, Delius H, Vogt B, Eilers M, Hatzigeorgiou A, Jansen-Durr P (1996) Cell cycle regulation of the murine cyclin E gene depends on an E2F binding site in the promoter. Mol. Cell. Biol. 16: 3401–3409.

    PubMed  CAS  Google Scholar 

  • Bremner R, Cohen BL, Sopta M, Hamel PA, Ingles CJ, Gallie BL, Phillips RA (1995) Direct transcriptional repression by pRB and its reversal by specific cyclins. Mol. Cell. Biol. 15: 3526–3265.

    Google Scholar 

  • Brook A, Xie J-E, Du W, Dyson N (1996) Requirements for dE2F function in proliferating cells and in post-mitotic differentiating cells. EMBO J. 15: 3676–3683.

    PubMed  CAS  Google Scholar 

  • Buchkovich K, Duffy LA, Harlow E (1989) The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell 58: 1097–1105.

    Article  PubMed  CAS  Google Scholar 

  • Buck V, Allen KE, Sorensen T, Bybee A, Hijmans EM, Voorhoeve PM, Bernards R, La Thangue NB, Sorensen T (1995) Molecular and functional characterisation of E2F-5, a new member of the E2F family. Oncogene 11: 31–38.

    PubMed  CAS  Google Scholar 

  • Campanero MR, Flemington EK (1997) Regulation of E2F through ubiquitin-proteasome-dependent degradation: Stabilization by the pRB tumor suppressor protein. Proc. Natl. Acad. Sci. USA 94: 2221–2226.

    Article  PubMed  CAS  Google Scholar 

  • Cao L, Faha B, Dembski M, Tsai L-H, Harlow E, Dyson N (1992) Independent binding of the retinoblastoma protein and p107 to the transcription factor E2F. Nature 355: 176–179.

    Article  PubMed  CAS  Google Scholar 

  • Chellappan S, Hiebert S, Mudryj M, Horowitz J, Nevins J (1991) The E2F transcription factor is a cellular target for the RB protein. Cell 65: 1053–1061.

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Saha P, Kornbluth S, Dynlacht BD, Dutta A (1996) Cyclin-binding motifs are essential for the function of p21CIPl. Mol. Cell. Biol. 16: 4673–4682.

    PubMed  CAS  Google Scholar 

  • Chen JD, Lin JY, Levine AJ (1995) Regulation of transcription functions of the p53 tumor suppressor by the mdm2 oncogene. Mol. Med. 1: 141–142.

    Google Scholar 

  • Chen P-L, Scully P, Shew J-Y, Wang J, Lee W-H (1989) Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. Cell 58: 1193–1198.

    Article  PubMed  CAS  Google Scholar 

  • Clarke A, Maandag E, van Roon M, van der Lugt N, van der Valk M, Hooper M, Berns A, te Riele H (1992) Requirement for a functional Rb-1 gene in murine development. Nature 359: 328–330.

    Article  PubMed  CAS  Google Scholar 

  • Claudio PP, De Luca A, Howard CM, Baldi A, Firpo EJ, Koff A, Paggi MG, Giordano A (1996) Functional analysis of pRb2/p130 interaction with cyclins. Cancer Res. 56: 2003–2008.

    PubMed  CAS  Google Scholar 

  • Cobrinik D, Whyte P, Peeper DS, Jacks T, Weinberg RA (1993) Cell cycle-specific association of E2F with the p130 E1A-binding domain. Genes Dev. 7: 2392–2404.

    Article  PubMed  CAS  Google Scholar 

  • Cobrinik D, Lee M-H, 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 

  • Connell-Crowley L, Harper JW, Goodrich DW (1997) Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. Mol. Biol. Cell. 8: 287–301.

    PubMed  CAS  Google Scholar 

  • Cress WD, Nevins JR (1996) A role for a bent DNA structure in E2F-mediated transcriptional activation. Mol. Cell. Biol. 16: 2119–2127.

    PubMed  CAS  Google Scholar 

  • Dagnino L, Fry CJ, Bartley SM, Farnham P, Gallie BL, Phillips RA (1997) Expression patterns of the E2F family of transcription factors during murine epithelial development. Cell Growth Diff. 8: 553–563.

    PubMed  CAS  Google Scholar 

  • Dalton S (1992) Cell cycle regulation of the human cdc2 gene. EMBO J. 11: 1797–1804.

    PubMed  CAS  Google Scholar 

  • DeCaprio JA, Ludlow JW, Lynch D, Furukawa Y, Griffin J, Piwnica-Worms H, Huang CM, Livingston DM (1989) The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell 58: 1085–1095.

    Article  PubMed  CAS  Google Scholar 

  • DeGregori J, Kowalik T, Nevins J (1995a) Cellular targets for activation by the E2F1 transcription 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 

  • DeGregori J, Leone G, Miron A, Jakoi L, Nevins JR (1997) Distinct roles for E2F proteins in cell growth control and apoptosis. Proc. Natl. Acad. Sci. USA 94: 7245–7250.

    Article  PubMed  CAS  Google Scholar 

  • De la Luna S, Burden MJ, Lee C-W, La 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 

  • Devoto SH, Mudryj M, Pines J, Hunter T, Nevins JR (1992) A cyclin A-protein kinase complex possesses sequence-specific DNA binding activity: p33cdk2 is a component of the E2F-cyclin A complex. Cell 68: 167–176.

    Article  PubMed  CAS  Google Scholar 

  • Dobrowolski SF, Stacey DW, Harter ML, Stine JT, Hiebert SW (1994) An E2F dominant negative mutant blocks E1A induced cell cycle progression. Oncogene 9: 2605–2612.

    PubMed  CAS  Google Scholar 

  • Dou QP, Zhao S, Levin AH, Wang J, Helin K, Pardee AB (1994) G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter. J. Biol. Chem. 269: 1306–1313.

    PubMed  CAS  Google Scholar 

  • Du W, Vidal M, Xie J-E, Dyson N (1996a) RBF, a novel RB-related gene that regulates E2F activity and interacts with cyclin E in Drosophila. Genes Dev. 10: 1206–1218.

    Article  PubMed  CAS  Google Scholar 

  • Du W, Xie J-E, Dyson N (1996b) Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye. EMBO J. 15: 3684–3692.

    PubMed  CAS  Google Scholar 

  • Duronio RJ, O’Farrell PH (1995) Developmental control of the G1 to S transition in Drosophila; cyclin E is a limiting downstream target of E2F. Genes Dev. 9: 1456–1468.

    Article  PubMed  CAS  Google Scholar 

  • Duronio RJ, O’Farrell PH, Xie J-E, Brook A, Dyson N (1995) The transcription factor E2F is required for S phase during Drosophila embryogenesis. Genes Dev. 9: 1445–1455.

    Article  PubMed  CAS  Google Scholar 

  • Dynlacht BD, Brook A, Dembski MS, Yenush L, Dyson N (1994a) DNA-binding and trans-activation properties of Drosophila E2F and DP proteins. Proc. Natl. Acad. Sci. USA 91: 6359–6363.

    Article  PubMed  CAS  Google Scholar 

  • Dynlacht BD, Flores O, Lees JA, Harlow E (1994b) Differential regulation of E2F trans-activation by cyclin-cdk2 complexes. Genes Dev. 8: 1772–1786.

    Article  PubMed  CAS  Google Scholar 

  • Emili A, Ingles CJ (1995) Promoter-dependent photocross-linking of the acidic transcriptional activator E2F-1 to the TATA-binding protein. J. Biol. Chem. 270: 13674–13680.

    Article  PubMed  CAS  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 

  • Faha B, Ewen ME, Tsai L-H, Livingston DM, Harlow E (1992) Interaction between human cyclin A and adenovirus E1A-associated p107 protein. Science 255: 87–90.

    Article  PubMed  CAS  Google Scholar 

  • Fan J, Bertino JR (1997) Functional roles of E2F in cell cycle regulation. Oncogene 14: 1191–1200.

    Article  PubMed  CAS  Google Scholar 

  • Field SJ, Tsai F-Y, 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 

  • Flemington EK, Speck SH, Kaelin WG (1993) E2F-1 mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product. Proc. Natl. Acad. Sci. USA 90: 6914–6918.

    Article  PubMed  CAS  Google Scholar 

  • Fry CJ, Slansky JE, Farnham PJ (1997) Position-dependent transcriptional regulation of the murine dihydrofolate reductase promoter by the E2F transactivation domain. Mol. Cell. Biol. 17: 1966–1976.

    PubMed  CAS  Google Scholar 

  • Furukawa Y, Terui Y, Sakoe K, Ohta M, Saito M (1994) The role of cellular transcription factor E2F in the regulation of cdc2 mRNA expression and cell cycle control of human hematopoietic cells. J Biol. Chem. 269: 26249–26258.

    PubMed  CAS  Google Scholar 

  • Geng Y, Eaton EN, Picon M, Roberts JM, Lundberg AS, Gifford A, Sardet C, Weinberg RA (1996) Regulation of cyclin E transcription by E2Fs and retinoblastoma protein. Oricogene 12: 1173–1180.

    CAS  Google Scholar 

  • Ginsberg D, Vairo G, Chittenden T, Xiao ZX, Xu G, Wydner KL, DeCaprio JA, Lawrence JB, Livingston DM (1994) E2F-4, a new member of the E2F transcription factor family, interacts with p107. Genes Dev, 8: 2665–2679.

    Article  PubMed  CAS  Google Scholar 

  • Girling R, Partridge JF, Bandara LR, Burden N, Totty NF, Hsuan JJ, La Thangue NB (1993) A new component of the transcription factor DRTF1/E2F. Nature 362: 83–87.

    Article  PubMed  CAS  Google Scholar 

  • Gopalkrishnan RV, Dolle P, Mattei M-G, La Thangue NB, Kedinger C (1996) Genomic structure and developmental expression of the mouse cell cycle regulatory transcription factor DP1. Oncogene 13: 2671–2680.

    PubMed  CAS  Google Scholar 

  • Guy CT, Zhou W, Kaufman S, Robinson MO (1996) E2F-1 blocks terminal differentiation and causes proliferation in transgenic megakaryocytes. Mol. Cell. Biol. 16: 685–693.

    PubMed  CAS  Google Scholar 

  • Hagemeier C, Bannister AJ, Cook A, Kouzarides T (1993) The activation domain of transcription factor PU.l binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. Proc. Natl. Acad. Sci. USA 90: 1580–1584.

    Article  PubMed  CAS  Google Scholar 

  • Hamel PA, Gill RM, Phillips RA, Gallie BL (1992a) Regions controlling hyperphosphorylation and conformation of the retinoblastoma gene product are independent of domains required for transcriptional repression. Oncogene 7: 693–701.

    PubMed  CAS  Google Scholar 

  • Hamel PA, Gill RM, Phillips RA, Gallie BL (1992b) Transcriptional repression of the E2-containing promoters EIIaE, c-myc, and RB1 by the product of the RB1 gene. Mol. Cell. Biol. 12: 3431–3438.

    PubMed  CAS  Google Scholar 

  • Hannon GJ, Demetrick D, Beach D (1993) Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins. Genes Dev. 7: 2378–2391.

    Article  PubMed  CAS  Google Scholar 

  • Hao XF, Alphey L, Bandara LR, Lam EW-F, Glover D, La Thangue NB (1995) Functional conservation of the cell cycle-regulating transcription factor DRTF1/E2F and its pathway of control in Drosophila melanogaster. J. Cell Sci. 108: 2945–2954.

    PubMed  CAS  Google Scholar 

  • Harrison DJ, Hooper ML, Armstrong JF, Clarke AR (1995) Effects of heterozygosity for the Rb-1t19neo allele in the mouse. Oncogene 10: 1615–1620.

    PubMed  CAS  Google Scholar 

  • Hatakeyama M, Brill JA, Fink GR, Weinberg RA (1994) Collaboration of Gl cyclins in the functional inactivation of the retinoblastoma protein. Genes Dev. 8: 1759–1771.

    Article  PubMed  CAS  Google Scholar 

  • Hateboer G, Kerkhoven RM, Shvarts A, Bernards R, Beijersbergen RL (1996) Degradation of E2F by the ubiquitin-proteasome pathway: regulation by retinoblastoma family proteins and adenovirus transforming proteins. Genes Dev. 10: 2960–2970.

    Article  PubMed  CAS  Google Scholar 

  • Haupt Y, Maya R, Kazaz A, Oren M (1997) Mdm2 promotes the rapid degradation of p53. Nature 387: 296–299.

    Article  PubMed  CAS  Google Scholar 

  • Helin K, Harlow E (1994) Heterodimerization of the transcription factors E2F1 and DPI is required for binding to the adenovirus E4 (ORF6/7) protein. J. Virol. 68: 5027–5035.

    PubMed  CAS  Google Scholar 

  • Helin K, Lees JA, Vidal M, Dyson N, Harlow E, Fattaey A (1992) A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F. Cell 70: 337–350.

    Article  PubMed  CAS  Google Scholar 

  • Helin K, Harlow E, Fattaey AR (1993a) Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein. Mol. Cell. Biol. 13: 6501–6508.

    PubMed  CAS  Google Scholar 

  • Helin K, Wu C-L, Fattaey A, Lees J, Dynlacht B, Ngwu C, Harlow E (1993b) Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative transactivation. Genes Dev. 7: 1850–1861.

    Article  PubMed  CAS  Google Scholar 

  • Henglein B, Chenivesse X, Wang J, Eick D, Brechot C (1994) Structure and cell cycle-regulated transcription of the human cyclin A gene. Proc. Nat. Acad. Sci. USA 91: 5490–5494.

    Article  PubMed  CAS  Google Scholar 

  • Herrera RE, Sah VP, Williams BO, Makela TP, Weinberg RA, Jacks T (1996) Altered cell cycle kinetics, gene expression, and Gl restriction point regulation in Rb-deficient fibroblasts. Mol. Cell. Biol. 16: 2402–2407.

    PubMed  CAS  Google Scholar 

  • Hiebert SW, Lipp M, Nevins JR (1989) E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor. Proc. Natl. Acad. Sci. USA 86: 3594–3598.

    Article  PubMed  CAS  Google Scholar 

  • Hiebert SW, Blake M, Azizkhan J, Nevins JR (1991) Role of E2F transcription factor in E1A-mediated trans-activation of cellular genes. J. Virol. 65: 3547–3552.

    PubMed  CAS  Google Scholar 

  • Hiebert SW, Packham G, Strom DK, Haffner R, Oren M, Zambetti G, Cleveland JL (1995) E2F1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Mol. Cell. Biol. 15: 6864–6874.

    PubMed  CAS  Google Scholar 

  • Hijmans EM, Voorhoeve PM, Beijersbergen RL, van’t Veer L, Bernards R (1995) E2F-5, a new E2F family member that interacts with p130 in vivo. Mol. Cell. Biol. 15: 3082–3089.

    PubMed  CAS  Google Scholar 

  • Hofmann F, Livingston DM (1996) Differential effects of cdk2 and cdk3 on the control of pRB and E2F function during Gl exit. Genes Dev. 10: 851–861.

    Article  PubMed  CAS  Google Scholar 

  • Hofmann F, Martelli F, Livingston DM, Wang Z (1996) The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway. Genes Dev. 10: 2949–2959.

    Article  PubMed  CAS  Google Scholar 

  • Holmberg C, Helin K, Schested M, Karlstrom O (1998) E2F-1 induced p53-independent apoptosis in transgenic mice. Oncogene (in press).

    Google Scholar 

  • Horowitz JM, Udvadia AJ (1995) Transcriptional regulation by the retinoblastoma (Rb) protein. Mol. Cell. Diff. 3: 275–314.

    CAS  Google Scholar 

  • Hsiao K-M, McMahon SL, Farnham PJ (1994) Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes Dev. 8: 1526–1537.

    Article  PubMed  CAS  Google Scholar 

  • Hsieh J-K, 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 

  • Hu N, Gutsmann A, Herbert DC, Bradley A, Lee W-H, Lee EY (1994) Heterozygous Rb-1 delta 20/+mice are predisposed to tumors of the pituitary gland with a nearly complete penetrance. Oncogene 9: 1021–1027.

    PubMed  CAS  Google Scholar 

  • Huber HE, Edwards G, Goodhart PJ, Patrick DR, Huang PS, Ivey-Hoyle M, Barnett SF, Oliff A, Heimbrook DC (1993) Transcription factor E2F binds DNA as a heterodimer. Proc. Natl. Acad. Sci. USA 90: 3525–3529.

    Article  PubMed  CAS  Google Scholar 

  • Hurford R, Cobrinik D, Lee M-H, 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 M-A, Jakoi L, Nevins J (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 

  • Imperiale MJ, Kao HT, Feldman LT, Nevins JR, Strickland S (1984) Common control of the heat shock gene and early adenovirus genes: evidence for a cellular E1 A-like activity. Mol. Cell. Biol. 4: 867–874.

    PubMed  CAS  Google Scholar 

  • Ishizaki J, Nevins JR, Sullenger BA (1996) Inhibition of cell proliferation by an RNA ligand that selectively blocks E2F function. Nature Med. 2: 1386–1389.

    Article  PubMed  CAS  Google Scholar 

  • Ivey-Hoyle M, Conroy R, Huber H, Goodhart P, Oliff A, Heinbrook DC (1993) Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F. Mol. Cell Biol. 13: 7802–7812.

    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 [see comments]. Nature 359: 295–300.

    Article  PubMed  CAS  Google Scholar 

  • Johnson DG, Schwarz JK, Cress WD, Nevins JR (1993) Expression of transcription factor E2F1 induces quiescent cells to enter S phase. Nature 365: 349–352.

    Article  PubMed  CAS  Google Scholar 

  • Johnson DG, Cress WD, Jakoi L, Nevins JR (1994a) Oncogenic capacity of the E2F1 gene. Proc Natl Acad Sci USA 91: 12823–12827.

    Article  PubMed  CAS  Google Scholar 

  • Johnson DG, Ohtani K, Nevins JR (1994b) Autoregulatory control of E2F-1 expression in response to positive and negative regulators of cell cycle expression. Genes Dev. 8: 1514–1525.

    Article  PubMed  CAS  Google Scholar 

  • Jooss K, Lam EW-F, Bybee A, Girlin R, Muller R, La Thangue NB (1995) Proto-oncogenic properties of the DP family of proteins. Oncogene 10: 1529–1536.

    PubMed  CAS  Google Scholar 

  • Kaelin WG, Krek W, Sellers WR, DeCaprio JA, Ajchenbaum F, Fuchs CS, Chittenden T, Li Y, Farnham PJ, Blanar MA, Livingston DM, Flemington EK (1992) Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell 70: 351–364.

    Article  PubMed  CAS  Google Scholar 

  • Karlseder J, Rotheneder H, Wintersberger E (1996) Interaction of Sp1 with the growth-and cell cycle-regulated transcription factor E2F. Mol. Cell. Biol. 16: 1659–1667.

    PubMed  CAS  Google Scholar 

  • Kitagawa M, Higashi H, Suzuki-Takahashi I, Segawa K, Hanks SK, Taya Y, Nishimura S, Okuyama A (1995) Phosphorylation of E2F-1 by cyclin A-cdk2. Oncogene 10: 229–236.

    PubMed  CAS  Google Scholar 

  • Kovesdi I, Reichel R, Nevins JR (1986) Identification of a cellular transcription factor involved in E1A trans-activation. Cell 45: 219–228.

    Article  PubMed  CAS  Google Scholar 

  • Kowalik TF, DeGregori J, Schwarz JK, Nevins JR (1995) E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis. J. Virol. 69: 2491–2500.

    PubMed  CAS  Google Scholar 

  • Krek W, Livingston DM, Shirodkar S (1993) Binding to DNA and the retinoblastoma gene product promoted by complex formation of different E2F family members. Science 262: 1557–1560.

    Article  PubMed  CAS  Google Scholar 

  • Krek W, Ewen M, Shirodkar S, Arany Z, Kaelin WG, Livingston DM (1994) Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase. Cell 78: 161–172.

    Article  PubMed  CAS  Google Scholar 

  • Krek W, Xu G, Livingston DM (1995) Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint. Cell 83: 1149–1158.

    Article  PubMed  CAS  Google Scholar 

  • Kubbutat MH, Jones SP, Vousden KH (1997) Regulation of p53 stability by Mdm2. Nature 387: 299–303.

    Article  PubMed  CAS  Google Scholar 

  • La Thangue NB (1994) DTRF1/E2F: an extending family of heteridimeric factors implicated in cell cycle control. Trends Biochem. Sci. 19: 108–114.

    Article  PubMed  Google Scholar 

  • La Thangue NB, Rigby PWJ (1987) An adenovirus El A-like transcription factor is regulated during the differentiation of murine embryonal carcinoma stem cells. Cell 49: 507–513.

    Article  PubMed  Google Scholar 

  • Lam EW-F, Watson RJ (1993) An E2F-binding site mediates cell-cycle regulated repression of mouse B-myb transcription. EMBO J. 12: 2705–2713.

    PubMed  CAS  Google Scholar 

  • Lee EY-HP, Chang C-Y, Hu N, Wang Y-CJ, Lai C-C, Herrup K, Lee W-H, Bradley A (1992) Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359: 288–294.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lees JA, Saito M, Vidal M, Valentine M, Look T, Harlow E, Dyson N, Helin K (1993) The retinoblastoma protein binds to a family of E2F transcription factors. Mol. Cell. Biol. 13: 7813–7825.

    PubMed  CAS  Google Scholar 

  • Li L-J, Naeve GS, Lee AS (1993) Temporal regulation of cyclin A-p107 and p33cdk2 complexes binding to a human thymidine kinase promoter element important for G1-S phase transcriptional regulation. Proc. Natl. Acad. Sci. USA 91: 3554–3558.

    Article  Google Scholar 

  • Li Y, Graham C, Lacy S, Duncan AM, Whyte P (1993b) The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E. Genes Dev. 7: 2366–2377.

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Slansky JE, Myers DJ, Drinkwater NR, Kaelin WG, Farnham PJ (1994) Cloning, chromosomal location, and characterization of mouse E2F1. Mol Cell Biol. 14: 1861–1869.

    Article  PubMed  CAS  Google Scholar 

  • Lin S-Y, Black AR, Kostic D, Pajovic S, Hoover CN, Azizkhan JC (1996) Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction. Mol. Cell. Biol. 16: 1668–1675.

    PubMed  CAS  Google Scholar 

  • Lindeman GJ, Gaubatz S, Livingston DM, Ginsberg D (1997) The subcellular localization of E2F4 is cell-cycle dependent. Proc. Natl. Acad. Sci. USA 94: 5095–5100.

    Article  PubMed  CAS  Google Scholar 

  • Logan TJ, Evans DL, Mercer WE, Bjornsti MA, Hall DJ (1995) Expression of a deletion mutant of the E2F transcription factor in fibroblasts lengthens S phase and increase sensitivity to S phasespecific toxin. Cancer Res. 55: 2883–2891.

    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 

  • Lukas J, Petersen BO, Holm K, Bartek J, Helin K (1996) Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression. Mol. Cell. Biol. 16: 1047–1057.

    PubMed  CAS  Google Scholar 

  • Luo Y, Hurwitz J, Massague J (1995) Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cipl. Nature 375: 159–161.

    Article  PubMed  CAS  Google Scholar 

  • Maandag ECR, van der Valk M, Vlaar M, Feltkamp C, O’Brien J, Van Roon M, Van der Lugt N, Berns A, teRiele H (1994) Developmental rescue of an embryonic-lethal mutation in the retinoblastoma gene in chimeric mice. EMBO J. 13: 4260–4268.

    PubMed  CAS  Google Scholar 

  • Magae J, Wu C-L, 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 

  • Mann DJ, Jones NC (1996) E2F-1 but not E2F-4 can overcome p16-induced G1 cell cycle arrest. Curr. Biol. 6: 474–483.

    Article  PubMed  CAS  Google Scholar 

  • Martin K, Trouche D, Hagemeier C, Sorensen TS, La Thangue NB, Kouzarides T (1995) Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein. Nature 375: 691–694.

    Article  PubMed  CAS  Google Scholar 

  • Mayol X, Garriga J, Grana X (1995) Cell-cycle dependent phosphorylation of p130. Oncogene 11: 801–808.

    PubMed  CAS  Google Scholar 

  • Means AL, Slansky JE, McMahon SL, Knuth MW, Farnham PJ (1992) The HIP binding site is required for growth regulation of the dihydrofolate reductase promoter. Mol. Cell. Biol. 12: 1054–1063.

    PubMed  CAS  Google Scholar 

  • Melillo RM, Helin K, Lowy DR, Schiller JT (1994) Positive and negative regulation of cell proliferation by E2F-1: influence of protein level and human papillomavirus oncoproteins. Mol. Cell. Biol. 14: 8241–8249.

    PubMed  CAS  Google Scholar 

  • Miltenberger RJ, Sukow KA, Farnham PJ (1995) An E-box-mediated increase in cad transcription at the Gl/S-phase boundary is suppressed by inhibition by inhibitory c-myc mutants. Mol. Cell. Biol. 15: 2527–2535.

    PubMed  CAS  Google Scholar 

  • Mittnacht S, Weinberg RA (1991) Gl/S phosphorylation of the retinoblastoma protein is associated with altered affinity for the nuclear compartment. Cell 65: 381–393.

    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 

  • Moran E (1993) DNA tumor virus transforming proteins and the cell cycle. Curr. Opin. Genet. Dev. 3: 63–70.

    Article  PubMed  CAS  Google Scholar 

  • Mudryj M, Hiebert SW, Nevins JR (1990) A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. EMBO J. 9: 2179–2184.

    PubMed  CAS  Google Scholar 

  • Müller H, Lukas J, Schneider A, Warthoe P, Bartek J, Eilers M, Strauss M (1994) Cyclin D1 expression is regulated by the retinoblastoma protein. Proc. Natl. Acad. Sci. USA 91: 2945–2949.

    Article  PubMed  Google Scholar 

  • Müller H, Moroni MC, Vigo E, Petersen 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 

  • Neuman E, Flemington EK, Sellers WR, Kaelin WG (1994) Transcription of the E2F1 gene is rendered cell cycle-dependent by E2F DNA binding sites within its promoter. Mol. Cell. Biol. 14: 6607–6615.

    PubMed  CAS  Google Scholar 

  • Nevins JR (1992) E2F: A link between the Rb tumor suppressor protein and viral oncoproteins. Science 258: 424–429.

    Article  PubMed  CAS  Google Scholar 

  • Nip J, Strom DK, Fee BE, Zambetti G, Cleveland JL, Hiebert SW (1997) E2F-1 cooperates with topoisomerase II inhibition and DNA damage to selectively augment p53-independent apoptosis. Mol. Cell. Biol. 17: 1049–1056.

    PubMed  CAS  Google Scholar 

  • O’Connor DJ, Lam EW-F, Griffin S, Zhong S, Leighton LC, Burbidge SA, Lu X (1995) Physical and functional interactions between p53 and cell cycle co-operating transcription factors, E2F1 and DP1. EMBO J. 14: 6184–6192.

    PubMed  Google Scholar 

  • Obert S, O’Connor RJ, Schmid S, Hearing P (1994) The adenovirus E4-6/7 protein transactivates the E2 promoter by inducing dimerization of a heterodimeric E2F complex. Mol. Cell. Biol. 14: 1333–1346.

    PubMed  CAS  Google Scholar 

  • Ogris E, Rotheneder H, Mudrak I, Pichler A, Wintersberger E (1993) A binding site for transcription factor E2F is a target for transactivation of murine thymidine kinase by polyomavirus large T antigen and plays an important role in growth regulation of the gene. J Virol. 67: 1765–1771.

    PubMed  CAS  Google Scholar 

  • Ohtani K, Nevins JR (1994) Functional properties of a Drosophila homolog of the E2F1 gene. Mol. Cell. Biol. 14: 1603–1612.

    PubMed  CAS  Google Scholar 

  • Ohtani K, DeGregori J, Nevins JR (1995) Regulation of the cylcin E gene by transcription factor E2F1. Proc. Natl. Acad. Sci. USA 92: 12146–12150.

    Article  PubMed  CAS  Google Scholar 

  • Ohtani K, DeGregori J, Leone G, Herendeen DR, Kelly TJ, Nevins JR (1996) Expression of the HsOrcl gene, a human ORC1 homolog is regulated by cell proliferation via the E2F transcription factor. Mol. Cell. Biol. 16: 6977–6984.

    PubMed  CAS  Google Scholar 

  • Ormondroyd E, de la Luna S, La Thangue NB (1995) A new member of the DP family, DP-3, with distinct protein products suggests a regulatory role for alternative splicing in the cell cycle transcription factor DRTF1/E2F. Oncogene 11, 1437–1446.

    PubMed  CAS  Google Scholar 

  • Oswald F, Dobner T, Lipp M (1996) The E2F transcription factor activates a replication-dependent human H2A gene in early S phase of the cell cycle. Mol. Cell. Biol. 16: 1889–1895.

    PubMed  CAS  Google Scholar 

  • Pagano M, Draetta G, Jansen-Durr P (1992) Association of cdk2 kinase with the transcription factor E2F during S phase. Science 255: 1144–1147.

    Article  PubMed  CAS  Google Scholar 

  • Pasteau S, Loiseau L, Arnaud L, Trembleau A, Brun G (1995) Isolation and characterization of a chicken homolog of the E2F-1 transcription factor. Oncogene 11: 1475–1486.

    PubMed  CAS  Google Scholar 

  • Pearson BE, Nasheuer HP, Wang TS (1991) Human DNA polymerase alpha gene: Sequences controlling expression in cycling and serum-stumulated cells. Mol. Cell. Biol. 11: 2081–2095.

    PubMed  CAS  Google Scholar 

  • Peeper DS, Keblusek P, Helin K, Toebes M, van der Eb AJ, Zantema A (1995) Phosphorylation of a specific cdk site in E2F-1 affects its electrophoretic mobility and promotes pRB-binding in vitro. Oncogene 10: 39–48.

    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 

  • Philpott A, Friend SH (1994) E2F and its developmental regulation in Xenopus laevis. Mol. Cell. Biol. 14: 5000–5009.

    PubMed  CAS  Google Scholar 

  • Picksley SM, Lane DP (1993) The p53-mdm2 autoregulatory feedback loop-aparadigm for the regulation of growth control by p53? Bioessays 15: 689–690.

    Article  PubMed  CAS  Google Scholar 

  • Qin X-Q, Livingston DM, Kaelin WG, Adams P (1994) Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis. Proc. Natl. Acad. Sci. USA. 91: 10918–10922.

    Article  PubMed  CAS  Google Scholar 

  • Qin X-Q, Livingston DM, Ewen M, Sellers WR, Arany Z, Kaelin WG (1995) The transcription factor E2F-1 is a downstream target of RB action. Mol. Cell. Biol. 15: 742–755.

    PubMed  CAS  Google Scholar 

  • Riley DJ, Lee EY-HP, Lee W-H (1994) The retinoblastoma protein: more than a tumor suppressor. Annual Rev. Cell Biol. 10: 1–29.

    Article  CAS  Google Scholar 

  • Rogers KT, Higgins PDR, Milla MM, Phillips RS, Horowitz JM (1996) DP-2, a heterodimeric partner of E2F: Identification and characterization of DP-2 proteins expressed in vivo. Proc. Natl. Acad. Sci. USA 93: 7594–7599.

    Article  PubMed  CAS  Google Scholar 

  • Royzman I, Whittaker AJ, Orr-Weaver TL (1997) Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program. Genes Dev. 11: 1999–2011.

    Article  PubMed  CAS  Google Scholar 

  • Saha P, Eichbaum Q, Silberman ED, Mayer BJ, Dutta A (1997) p21Cipl and CDC25A: Competition between an inhibitor and an activator of cyclin-dependent kinases. Mol. Cell. Biol. 17: 4338–4345.

    PubMed  CAS  Google Scholar 

  • Saito M, Helin K, Valentine MB, Griffith BB, Willman CL, Harlow E, Look AT (1995) Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line. Genomics 25: 130–138.

    Article  PubMed  CAS  Google Scholar 

  • Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A, Weinberg RA (1995) E2F-4 and E2F-5, two novel 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 

  • Schulze A, Zerfass K, Spitkovsky D, Middendorp S, Berges J, Helin K, Jansen-Durr P, Henglein B (1995) Cell cycle regulation of the cyclin A gene promoter is mediated by a variant E2F site. Proc. Natl. Acad. Sci. USA 92: 11264–11268.

    Article  PubMed  CAS  Google Scholar 

  • Schwarz JK, Devoto SH, Smith EJ, Chellappan SP, Jakoi L, Nevins JR (1993) Interactions of the p107 and Rb proteins with E2F during the cell proliferation response. EMBO J. 12: 1013–1020.

    PubMed  CAS  Google Scholar 

  • Sears R, Ohtani K, Nevins JR (1997) Identification 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, Rodgers JW, Kaelin WG (1995) A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites. Proc. Natl. Acad. Sci. USA 92: 11544–11548.

    Article  PubMed  CAS  Google Scholar 

  • Seum C, Spierer A, Pauli D, Szidonya J, Reuter G, Spierer P (1996) Position-effect variegation in Drosophila depends on the dose of the gene encoding the E2F transcriptional activator and cell cycle regulator. Development 122: 1949–1956.

    PubMed  CAS  Google Scholar 

  • Shan B, Zhu X, Chen P-L, Durfee T, Yang Y, Sharp D, Lee W-H (1992) Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F. Mol. Cell. Biol. 12: 5620–5631.

    PubMed  CAS  Google Scholar 

  • Shan B, Lee W-H (1994) Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis. Mol. Cell. Biol. 14: 8166–8173.

    PubMed  CAS  Google Scholar 

  • Shan B, Farmer AA, Lee W-H (1996) The molecular basis of E2F-l/DP-l-induced S-phase entry and apoptosis. Cell Growth Diff. 7: 689–697.

    PubMed  CAS  Google Scholar 

  • Shirodkar S, Ewen M, DeCaprio JA, Morgan D, Livingston DM, Chittenden T (1992) The transcription factor E2F interacts with the retinoblastoma product and a p107-cyclin A complex in a cell cycle-regulated manner. Cell 68: 157–166.

    Article  PubMed  CAS  Google Scholar 

  • Singh P, Wong SH, Hong W (1994) Overexpression of E2F-1 in rat embryo fibroblasts leads to neoplastic transformation. EMBO J. 13: 3329–3338.

    PubMed  CAS  Google Scholar 

  • Slansky J, Li Y, Kaelin WG, Farnham PJ (1993) A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter. Mol. Cell. Biol. 13: 1610–1618.

    PubMed  CAS  Google Scholar 

  • Slansky JE and Farnham PJ (1996) Transcriptional control of cell growth: the E2F gene family. Curr. Top. Microbiol. and Immunol. (1996) 208: 1–30.

    Article  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Sorensen TS, Girling R, Lee CW, Gannon J, Bandara LR, La Thangue NB (1996) Functional interaction between DP-1 and p53. Mol. Cell. Biol. 16: 5888–5895.

    PubMed  CAS  Google Scholar 

  • Souza RF, Yin J, Smolinski KN, Zou T-T, Wang S, Shi Y-Q, Rhyu M-G, Cottrell J, Abraham JM, Biden K, Simms L, Leggett B, Bova GS, Frank T, Powell SM, Sugimura H, Young J, Harpaz N, Shimizu K, Matsubara N, Meltzer SJ (1997) Frequent mutation of the E2F-4 cell cycle gene in primary human gastrointestinal tumors. Cancer Res. 57: 2350–2353.

    PubMed  CAS  Google Scholar 

  • Studbal H, Zalvide J, DeCaprio JA (1996) Simian Virus 40 Large T antigen alters the phosphorylation state of the RB-related proteins p130 and p107. J. Virol. 70: 2781–2788.

    Google Scholar 

  • Suzuki-Takahasi I, Kitagawa M, Saijo M, Higashi H, Ogino H, Matsumoto H, Taya Y, Nishimura S, Okuyama A (1995) The interactions of E2F with pRB and with p107 are regulated via the phosphorylation of pRB and p107 by a cyclin-dependent kinase. Oncogene 10: 1691–1698.

    Google Scholar 

  • Tao Y, Kassatly RF, Cress WD, Horowitz JM (1997) Subunit composition determines E2F DNA-binding site specificity. Mol. Cell. Biol. 17 (12): 6994–7007.

    PubMed  CAS  Google Scholar 

  • Tevosian SG, Paulson KE, Bronson R, Yee AS (1996) Expression of the E2F-1/DP-1 transcription factor in murine development. Cell Growth Diff. 7: 43–52.

    PubMed  CAS  Google Scholar 

  • Thalmeier K, Synovzik H, Mertz R, Winnacker E-L, Lipp M (1989) Nuclear factor E2F mediates basic transcription and trans-activation by E1a of the human MYC promoter. Genes Dev. 3: 527–536.

    Article  PubMed  CAS  Google Scholar 

  • Thelander M, Thelander L (1989) Molecular cloning and expression of the functional gene encoding the M2 subunit of mouse ribonucleotide reductase: a new dominant marker gene. EMBO J. 8: 2475–2479.

    PubMed  CAS  Google Scholar 

  • Thut CJ, Goodrich JA, Tjian R (1997) Repression of p53-mediated transcription by MDM2: a dual mechanism. Genes Dev. 11: 1974–1986.

    Article  PubMed  CAS  Google Scholar 

  • Trouche D, Kouzarides T (1996) E2F1 and E1A 12S have a homologous activation domain regulated by RB and CBP. Proc. Natl. Acad. Sci. USA 93: 1439–1442.

    Article  PubMed  CAS  Google Scholar 

  • Vairo G, Livingston DM, Ginsberg D (1995) Functional interaction between E2F-4 and p130: evidence for distinct mechanisms underlying growth suppression by different retinoblastoma protein family members. Genes Dev. 9: 869–881.

    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 changes in subcellular localization. Mol. Cell Biol. 17: 7268–7282.

    PubMed  CAS  Google Scholar 

  • Weintraub SJ, Prater CA, Dean DC (1992) Retinoblastoma protein switches the E2F site from positive to negative element. Nature 358: 259–261.

    Article  PubMed  CAS  Google Scholar 

  • Weintraub SJ, Chow KNB, Luo RX, Zhang SH, He S, Dean DC (1995) Mechanism of active transcriptional repression by the retinoblastoma protein. Nature 375: 812–815.

    Article  PubMed  CAS  Google Scholar 

  • Wells J, Held P, Illenye S, Heintz NH (1996) Protein-DNA interactions at the major and minor promoters of the divergently transcribed dhfr and rep3 genes during the Chinese hamster ovary cell cycle. Mol. Cell. Biol. 16: 634–647.

    PubMed  CAS  Google Scholar 

  • Wu C-L, Zukerberg LR, Ngwu C, Harlow E, Lees JA (1995) In vivo association of E2F and DP family proteins. Mol. Cell. Biol. 15: 2536–2546.

    PubMed  CAS  Google Scholar 

  • Wu C-L, Classon M, Dyson N, Harlow E (1996) Expression of dominant-negative mutant DP-1 blocks cell cycle progression in Gl. Mol. Cell. Biol. 16: 3698–3706.

    PubMed  CAS  Google Scholar 

  • Wu X, Levine AJ (1994) p53 and E2F-1 cooperate to mediate apoptosis. Proc. Natl. Acad. Sci. USA 91: 3602–3606.

    Article  PubMed  CAS  Google Scholar 

  • Xu G, Livingston DM, Krek W (1995) Multiple members of the E2F transcription factor family are the products of oncogenes. Proc. Natl. Acad. Sci. USA 92: 1357–1361.

    Article  PubMed  CAS  Google Scholar 

  • Xu M, Sheppard KA, Peng CY, Yee AS, Piwnica-Worms H (1994) Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation. Mol. Cell. Biol. 14: 8420–8431.

    PubMed  CAS  Google Scholar 

  • Yagi H, Kato T, Nagata T, Habu T, Nozaki M, Matsushiro A, Nishimune Y, Morita T (1995) Regulation of the mouse histone H2A.X gene promoter by the transcription factor E2F and CCAAT binding protein. J. Biol. Chem. 270: 18759–18765.

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi M, Hayashi Y, Hirose F, Matsuoka S, Shiroki K, Matsukage A (1992) Activation of the mouse proliferating cell nuclear antigen gene promoter by adenovirus type 12 E1A proteins. Japan J. Canc. Res. 83: 609–617.

    Article  CAS  Google Scholar 

  • Yamaguchi M, Hayashi Y, Matsukage A (1995) Essential role of E2F recognition sites in regulation of the proliferating cell nuclear antigen gene promoter during Drosophila development. J. Biol. Chem. 270: 25159–25165.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Yamasaki L, Bronson R, Williams BO, Dyson NJ, Harlow E, Jacks T (1998) Loss of E2F-1 reduces tumorigenesis and extends lifespan of Rb(+/-) mice. Nature Genetics (in press).

    Google Scholar 

  • Zhang Y, Chellappan SP (1995) Cloning and characterization of human DP2, a novel dimerization partner of E2F. Oncogene 10: 2085–2093.

    PubMed  CAS  Google Scholar 

  • Zhu L, Harlow E, Dynlacht BD (1995a) p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F. Genes Dev. 9: 1740–1752.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Zwicker J, Muller R (1997) Cell-cycle regulation of gene expression by transcriptional repression. Trends Genet. 13: 3–6.

    Article  PubMed  CAS  Google Scholar 

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Yamasaki, L. (1998). Growth Regulation by the E2F and DP Transcription Factor Families. In: Pagano, M. (eds) Cell Cycle Control. Results and Problems in Cell Differentiation, vol 22. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69686-5_9

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