Skip to main content
SpringerLink
Log in

Interplay Between Cyclin-Dependent Kinases and E2F-Dependent Transcription

  • Chapter
  • First Online:
Cell Cycle Deregulation in Cancer

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Precise control of cell proliferation is essential for normal development and survival of all multi-cellular organisms. The deregulation of cell proliferation is a fundamental feature of all types of cancer. One of the key regulators of cell proliferation is the E2F transcription factor. E2F controls the expression of many genes that are required for cells to divide and elevated E2F activity is found in most tumor cells. The activation and inactivation of E2F are tightly linked to the activation of cyclin-dependent kinases (CDKs). In normal cells, these connections allow the periodic oscillations in CDK cycle to be coupled with temporal programs of gene expression. Multiple CDK–cyclin complexes (including CDK1/2–CycA, CDK1/2–CycB, and CDK7–CycH) have been shown to directly phosphorylate E2F or its dimerization partner DP. However, in recent genetic studies, one of the strongest modifiers of E2F-dependent phenotypes was cdk8, a kinase that had not previously been linked to E2F. In this review, we summarize the effects of CDKs on E2F1 activity and describe a model that may explain the role of CDK8–CycC in E2F regulation. Since CDKs can both increase and decrease E2F activity, understanding the interplay between E2F and CDK–cyclin complexes may suggest therapeutic approaches to efficiently block cancer cell proliferation.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

References

  • Akoulitchev S, Chuikov S, Reinberg D (2000) TFIIH is negatively regulated by cdk8-containing mediator complexes. Nature 407: 102–106.

    Article  PubMed  CAS  Google Scholar 

  • Ansari AZ, Koh SS, Zaman Z, et al. (2002) Transcriptional activating regions target a cyclin-dependent kinase. Proc Natl Acad Sci U S A 99: 14706–14709.

    Article  PubMed  CAS  Google Scholar 

  • Attwooll C, Lazzerini Denchi E, Helin K (2004) The E2F family: specific functions and overlapping interests. EMBO J 23: 4709–4716.

    Article  PubMed  CAS  Google Scholar 

  • Barski A, Cuddapah S, Cui K, et al. (2007) High-resolution profiling of histone methylations in the human genome. Cell 129: 823–837.

    Article  PubMed  CAS  Google Scholar 

  • Bjorklund S, Gustafsson CM (2005) The yeast Mediator complex and its regulation. Trends Biochem Sci 30: 240–244.

    Article  PubMed  CAS  Google Scholar 

  • Botz J, Zerfass-Thome K, Spitkovsky D, et al. (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 

  • Boube M, Joulia L, Cribbs DL, et al. (2002) Evidence for a mediator of RNA polymerase II transcriptional regulation conserved from yeast to man. Cell 110: 143–151.

    Article  PubMed  CAS  Google Scholar 

  • Bracken AP, Ciro M, Cocito A, et al. (2004) E2F target genes: unraveling the biology. Trends Biochem Sci 29: 409–417.

    Article  PubMed  CAS  Google Scholar 

  • Burkhart DL, Sage J (2008) Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat Rev Cancer 8: 671–682.

    Article  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 U S A 94: 2221–2226.

    Article  PubMed  CAS  Google Scholar 

  • Chen HH, Wang YC, Fann MJ (2006) Identification and characterization of the CDK12/cyclin L1 complex involved in alternative splicing regulation. Mol Cell Biol 26: 2736–2745.

    Article  PubMed  CAS  Google Scholar 

  • Chen HH, Wong YH, Geneviere AM, et al. (2007) CDK13/CDC2L5 interacts with L-type cyclins and regulates alternative splicing. Biochem Biophys Res Commun 354: 735–740.

    Article  PubMed  CAS  Google Scholar 

  • Chi Y, Huddleston MJ, Zhang X, et al. (2001) Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. Genes Dev 15: 1078–1092.

    Article  PubMed  CAS  Google Scholar 

  • Classon M, Dyson N (2001) p107 and p130: versatile proteins with interesting pockets. Exp Cell Res 264: 135–147.

    Article  PubMed  CAS  Google Scholar 

  • Conaway RC, Sato S, Tomomori-Sato C, et al. (2005) The mammalian Mediator complex and its role in transcriptional regulation. Trends Biochem Sci 30: 250–255.

    Article  PubMed  CAS  Google Scholar 

  • DeGregori J, Kowalik T, Nevins JR (1995) 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, Johnson DG (2006) Distinct and Overlapping Roles for E2F Family Members in Transcription, Proliferation and Apoptosis. Curr Mol Med 6: 739–748.

    PubMed  CAS  Google Scholar 

  • Dimova DK, Dyson NJ (2005) The E2F transcriptional network: old acquaintances with new faces. Oncogene 24: 2810–2826.

    Article  PubMed  CAS  Google Scholar 

  • Donner AJ, Szostek S, Hoover JM, et al. (2007) DK8 is a stimulus-specific positive coregulator of p53 target genes. Mol Cell 27: 121–133.

    Article  PubMed  CAS  Google Scholar 

  • Dou Y, Milne TA, Tackett AJ, et al. (2005) Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 121: 873–885.

    Article  PubMed  CAS  Google Scholar 

  • Duronio RJ, O’Farrell PH, Xie JE, et al. (1995) The transcription factor E2F is required for S phase during Drosophila embryogenesis. Genes Dev 9: 1445–1455.

    Article  PubMed  CAS  Google Scholar 

  • Dyer MA, Bremner R (2005) The search for the retinoblastoma cell of origin. Nat Rev Cancer 5: 91–101.

    PubMed  CAS  Google Scholar 

  • Dynlacht BD, Flores O, Lees JA, et al. (1994) Differential regulation of E2F transactivation by cyclin/cdk2 complexes. Genes Dev 8: 1772–1786.

    Article  PubMed  CAS  Google Scholar 

  • Dynlacht BD, Moberg K, Lees JA, et al. (1997) Specific regulation of E2F family members by cyclin-dependent kinases. Mol Cell Biol 17: 3867–3875.

    PubMed  CAS  Google Scholar 

  • Dyson N (1998) The regulation of E2F by pRB-family proteins. Genes Dev 12: 2245–2262.

    Article  PubMed  CAS  Google Scholar 

  • Elmlund H, Baraznenok V, Lindahl M, et al. (2006) The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II. Proc Natl Acad Sci U S A 103: 15788–15793.

    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 

  • Firestein R, Bass AJ, Kim SY, et al. (2008) CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature 455: 547–551.

    Article  PubMed  CAS  Google Scholar 

  • Fisher RP (2005) Secrets of a double agent: CDK7 in cell-cycle control and transcription. J Cell Sci 118: 5171–5180.

    Article  PubMed  CAS  Google Scholar 

  • Frolov MV, Dyson NJ (2004) Molecular mechanisms of E2F-dependent activation and pRB-mediated repression. J Cell Sci 117: 2173–2181.

    Article  PubMed  CAS  Google Scholar 

  • Fry CJ, Pearson A, Malinowski E, et al. (1999) Activation of the murine dihydrofolate reductase promoter by E2F1. A requirement for CBP recruitment. J Biol Chem 274: 15883–15891.

    Article  PubMed  CAS  Google Scholar 

  • Fryer CJ, White JB, Jones KA (2004) Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 16: 509–520.

    Article  PubMed  CAS  Google Scholar 

  • Geng Y, Eaton EN, Picon M, et al. (1996) Regulation of cyclin E transcription by E2Fs and retinoblastoma protein. Oncogene 12: 1173–1180.

    PubMed  CAS  Google Scholar 

  • Gope R, Christensen MA, Thorson A, et al. (1990) Increased expression of the retinoblastoma gene in human colorectal carcinomas relative to normal colonic mucosa. J Natl Cancer Inst 82: 310–314.

    Article  PubMed  CAS  Google Scholar 

  • Greenman C, Stephens P, Smith R, et al. (2007) Patterns of somatic mutation in human cancer genomes. Nature 446: 153–158.

    Article  PubMed  CAS  Google Scholar 

  • Haase SB, Reed SI (1999) Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle. Nature 401: 394–397.

    PubMed  CAS  Google Scholar 

  • Hallberg M, Polozkov GV, Hu GZ, et al. (2004) Site-specific Srb10-dependent phosphorylation of the yeast Mediator subunit Med2 regulates gene expression from the 2-microm plasmid. Proc Natl Acad Sci USA. 101: 3370–3375.

    Article  PubMed  CAS  Google Scholar 

  • Hagemeier C, Cook A, Kouzarides T (1993) The retinoblastoma protein binds E2F residues required for activation in vivo and TBP binding in vitro. Nucleic Acids Res 21: 4998–5004.

    Article  PubMed  CAS  Google Scholar 

  • Hahn S (2004) Structure and mechanism of the RNA polymerase II transcription machinery. Nat Struct Mol Biol 11: 394–403.

    Article  PubMed  CAS  Google Scholar 

  • Hateboer G, Kerkhoven RM, Shvarts A, et al. (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 

  • Hengartner CJ, Myer VE, Liao SM, et al. (1998) Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. Mol Cell 2: 43–53.

    Article  PubMed  CAS  Google Scholar 

  • Hériché JK, Ang D, Bier E, et al. (2003) Involvement of an SCFSlmb complex in timely elimination of E2F upon initiation of DNA replication in Drosophila. BMC Genet 4: 9.

    Article  PubMed  Google Scholar 

  • Hirst M, Kobor MS, Kuriakose N, et al. (1999) GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8. Mol Cell 3: 673–678.

    Article  PubMed  CAS  Google Scholar 

  • Hofmann F, Martelli F, Livingston DM, et al. (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 

  • Hsiao KM, 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 

  • Ianari A, Gallo R, Palma M, et al. (2004) Specific role for p300/CREB-binding protein-associated factor activity in E2F1 stabilization in response to DNA damage. J Biol Chem 279: 30830–30835.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Johnson DG, Degregori J (2006) Putting the Oncogenic and Tumor Suppressive Activities of E2F into Context. Curr Mol Med 6: 731–738.

    PubMed  CAS  Google Scholar 

  • Kitagawa M, Higashi H, Suzuki-Takahashi I, et al. (1995) Phosphorylation of E2F-1 by cyclin A-cdk2. Oncogene 10: 229–236.

    PubMed  CAS  Google Scholar 

  • Knez J, Piluso D, Bilan P, et al. (2006) Host cell factor-1 and E2F4 interact via multiple determinants in each protein. Mol Cell Biochem 288: 79–90.

    Article  PubMed  CAS  Google Scholar 

  • Knuesel MT, Meyer KD, Donner AJ, et al. (2009a) The human CDK8 subcomplex is a histone kinase that requires Med12 for activity and can function independently of mediator. Mol Cell Biol 29: 650–661.

    Article  PubMed  CAS  Google Scholar 

  • Knuesel MT, Meyer KD, Bernecky C, et al. (2009b) The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function. Genes Dev 23: 439–451.

    Article  PubMed  CAS  Google Scholar 

  • Kornberg RD (2005) Mediator and the mechanism of transcriptional activation. Trends Biochem Sci 30: 235–239.

    Article  PubMed  CAS  Google Scholar 

  • Krek W, Ewen ME, Shirodkar S, et al. (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 

  • Lang SE, McMahon SB, Cole MD, et al. (2001) E2F transcriptional activation requires TRRAP and GCN5 cofactors. J Biol Chem 276: 32627–32634.

    Article  PubMed  CAS  Google Scholar 

  • Lee MG, Nurse P (1987) Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature 327: 31–35.

    Article  PubMed  CAS  Google Scholar 

  • Lee RJ, Albanese C, Fu M, et al. (2000) Cyclin D1 is required for transformation by activated Neu and is induced through an E2F-dependent signaling pathway. Mol Cell Biol 20: 672–683.

    Article  PubMed  CAS  Google Scholar 

  • Li H, Lahti JM, Valentine M, et al. (1996) Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: deletion of the CCNC gene in human tumors. Genomics 32: 253–259.

    Article  PubMed  CAS  Google Scholar 

  • Lin WC, Lin FT, Nevins JR (2001) Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev 15: 1833–1844.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lipinski MM, Jacks T (1999) The retinoblastoma gene family in differentiation and development. Oncogene 18: 7873–7882.

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Kipreos ET (2000) Evolution of cyclin-dependent kinases (CDKs) and CDK-activating kinases (CAKs): differential conservation of CAKs in yeast and metazoa. Mol Biol Evol 17: 1061–1074.

    PubMed  CAS  Google Scholar 

  • Liu Y, Kung C, Fishburn J, et al. (2004) Two cyclin-dependent kinases promote RNA polymerase II transcription and formation of the scaffold complex. Mol Cell Biol 24: 1721–1735.

    Article  PubMed  CAS  Google Scholar 

  • Loyer P, Trembley JH, Katona R, et al. (2005) Role of CDK/cyclin complexes in transcription and RNA splicing. Cell Signal 17: 1033–1051.

    Article  PubMed  CAS  Google Scholar 

  • Luciano RL, Wilson AC (2003) HCF-1 functions as a coactivator for the zinc finger protein Krox20. J Biol Chem 278: 51116–51124.

    Article  PubMed  CAS  Google Scholar 

  • Maiti B, Li J, de Bruin A, et al. (2005) Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferation. J Biol Chem 280: 18211–18220.

    Article  PubMed  CAS  Google Scholar 

  • Majello B, Napolitano G, De Luca P, et al. (1998) Recruitment of human TBP selectively activates RNA polymerase II TATA-dependent promoters. J Biol Chem 273: 16509–16516.

    Article  PubMed  CAS  Google Scholar 

  • Malik S, Guermah M, Yuan CX, et al. (2004) Structural and functional organization of TRAP220, the TRAP/mediator subunit that is targeted by nuclear receptors. Mol Cell Biol 24: 8244–8254.

    Article  PubMed  CAS  Google Scholar 

  • Malik S, Roeder RG (2005) Dynamic regulation of pol II transcription by the mammalian Mediator complex. Trends Biochem Sci 30: 256–263.

    Article  PubMed  CAS  Google Scholar 

  • Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9: 153–166.

    Article  PubMed  CAS  Google Scholar 

  • Marti A, Wirbelauer C, Scheffner M, et al. (1999) Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation. Nat Cell Biol 1: 14–19.

    Article  PubMed  CAS  Google Scholar 

  • Martínez-Balbás MA, Bauer UM, Nielsen SJ, et al. (2000) Regulation of E2F1 activity by acetylation. EMBO J 19: 662–671.

    Article  PubMed  CAS  Google Scholar 

  • Milton A, Luoto K, Ingram L, et al. (2006) A functionally distinct member of the DP family of E2F subunits. Oncogene 25: 3212–3218.

    Article  PubMed  CAS  Google Scholar 

  • Mittler G, Kremmer E, Timmers HT, et al. (2001) Novel critical role of a human Mediator complex for basal RNA polymerase II transcription. EMBO Rep 2: 808–813.

    Article  PubMed  CAS  Google Scholar 

  • Moroni MC, Hickman ES, Lazzerini Denchi E, et al. (2001) Apaf-1 is a transcriptional target for E2F and p53. Nat Cell Biol 3: 552–558.

    Article  PubMed  CAS  Google Scholar 

  • Morris EJ, Ji JY, Yang F, et al. (2008) E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8. Nature 455: 552–556.

    Article  PubMed  CAS  Google Scholar 

  • Müller H, Helin K (2000) The E2F transcription factors: key regulators of cell proliferation. Biochim Biophys Acta 1470: M1–M12.

    Google Scholar 

  • Müller H, Bracken AP, Vernell R, et al. (2001) E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. Genes Dev 15: 267–285.

    Article  PubMed  CAS  Google Scholar 

  • Myers LC, Kornberg RD (2000) Mediator of transcriptional regulation. Annu Rev Biochem 69: 729–749.

    Article  PubMed  CAS  Google Scholar 

  • Näär AM, Lemon BD, Tjian R (2001) Transcriptional coactivator complexes. Annu Rev Biochem 70: 475–501.

    Article  PubMed  CAS  Google Scholar 

  • Näär AM, Taatjes DJ, Zhai W, et al. (2002) Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation. Genes Dev 16: 1339–1344.

    Article  PubMed  CAS  Google Scholar 

  • Nasmyth K (1995) Evolution of the cell cycle. Philos Trans R Soc Lond B Biol Sci 349: 271–281.

    Article  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 

  • Nevins JR (1998) Toward an understanding of the functional complexity of the E2F and retinoblastoma families. Cell Growth Differ 9: 585–593.

    PubMed  CAS  Google Scholar 

  • Nevins JR (2001) The Rb/E2F pathway and cancer. Hum Mol Genet 10: 699–703.

    Article  PubMed  CAS  Google Scholar 

  • Nurse P (1990) Universal control mechanism regulating onset of M-phase. Nature 344: 503–508.

    Article  PubMed  CAS  Google Scholar 

  • Nurse P (2000) A long twentieth century of the cell cycle and beyond. Cell 100: 71–78.

    Article  PubMed  CAS  Google Scholar 

  • Ohata N, Ito S, Yoshida A, et al. (2006) Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: involvement of cyclin C in osteosarcoma. Int J Mol Med 18: 1153–1158.

    PubMed  CAS  Google Scholar 

  • Ohta T, Xiong Y (2001) Phosphorylation- and Skp1-independent in vitro ubiquitination of E2F1 by multiple ROC-cullin ligases. Cancer Res 61: 1347–1353.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Orlando DA, Lin CY, Bernard A, et al. (2008) Global control of cell-cycle transcription by coupled CDK and network oscillators. Nature 453: 944–947.

    Article  PubMed  CAS  Google Scholar 

  • Pearson A, Greenblatt J (1997) Modular organization of the E2F1 activation domain and its interaction with general transcription factors TBP and TFIIH. Oncogene 15: 2643–2658.

    Article  PubMed  CAS  Google Scholar 

  • Pediconi N, Ianari A, Costanzo A, et al. (2003) Differential regulation of E2F1 apoptotic target genes in response to DNA damage. Nat Cell Biol 5: 552–558.

    Article  PubMed  CAS  Google Scholar 

  • Peeper DS, Keblusek P, Helin K, et al. (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 

  • Phatnani HP, Greenleaf AL (2006) Phosphorylation and functions of the RNA polymerase II CTD. Genes Dev 20: 2922–2936.

    Article  PubMed  CAS  Google Scholar 

  • Ren B, Cam H, Takahashi Y, et al. (2002) E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. Genes Dev 16: 245–256.

    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 

  • Samuelsen CO, Baraznenok V, Khorosjutina O, et al. (2003) TRAP230/ARC240 and TRAP240/ARC250 Mediator subunits are functionally conserved through evolution. Proc Natl Acad Sci U S A 100: 6422–6427.

    Article  PubMed  CAS  Google Scholar 

  • Schulman BA, Lindstrom DL, Harlow E (1998) Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. Proc Natl Acad Sci U S A 95: 10453–10458.

    Article  PubMed  CAS  Google Scholar 

  • Schulze A, Zerfass K, Spitkovsky D, et al. (1995) Cell cycle regulation of the cyclin A gene promoter is mediated by a variant E2F site. Proc Natl Acad Sci U S A 92: 11264–11268.

    Article  PubMed  CAS  Google Scholar 

  • Shan B, Farmer AA, Lee WH (1996) The molecular basis of E2F-1/DP-1-induced S-phase entry and apoptosis. Cell Growth Differ 7: 689–697.

    PubMed  CAS  Google Scholar 

  • Sherr CJ (1996) Cancer cell cycles. Science 274: 1672–1677.

    Article  PubMed  CAS  Google Scholar 

  • Shibutani ST, de la Cruz AF, Tran V, et al. (2008) Intrinsic negative cell cycle regulation provided by PIP box- and Cul4Cdt2-mediated destruction of E2f1 during S phase. Dev Cell 15: 890–900.

    Article  PubMed  CAS  Google Scholar 

  • Shimizu M, Ichikawa E, Inoue U, et al. (1995) The G1/S boundary-specific enhancer of the rat cdc2 promoter. Mol Cell Biol 15: 2882–2892.

    PubMed  CAS  Google Scholar 

  • Smith ER, Cayrou C, Huang R, et al. (2005) A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16. Mol Cell Biol 25: 9175–9188.

    Article  PubMed  CAS  Google Scholar 

  • Stevaux O, Dyson NJ (2002) A revised picture of the E2F transcriptional network and RB function. Curr Opin Cell Biol 14: 684–691.

    Article  PubMed  CAS  Google Scholar 

  • Stevens C, Smith L, La Thangue NB (2003) Chk2 activates E2F-1 in response to DNA damage. Nat Cell Biol 5: 401–409.

    Article  PubMed  CAS  Google Scholar 

  • Su AI, Wiltshire T, Batalov S, et al. (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci U S A 101: 6062–6067.

    Article  PubMed  CAS  Google Scholar 

  • Taatjes DJ, Naar AM, Andel F, 3rd, et al. (2002) Structure, function, and activator-induced conformations of the CRSP coactivator. Science 295: 1058–1062.

    Article  PubMed  CAS  Google Scholar 

  • Taatjes DJ, Marr MT, Tjian R (2004) Regulatory diversity among metazoan co-activator complexes. Nat Rev Mol Cell Biol 5: 403–410.

    Article  PubMed  CAS  Google Scholar 

  • Tansey WP (2001) Transcriptional activation: risky business. Genes Dev 15: 1045–1050.

    Article  PubMed  CAS  Google Scholar 

  • Taubert S, Gorrini C, Frank SR, et al. (2004) E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G1. Mol Cell Biol 24: 4546–4556.

    Article  PubMed  CAS  Google Scholar 

  • Tommasi S, Pfeifer GP (1995) In vivo structure of the human cdc2 promoter: release of a p130-E2F-4 complex from sequences immediately upstream of the transcription initiation site coincides with induction of cdc2 expression. Mol Cell Biol 15: 6901–6913.

    PubMed  CAS  Google Scholar 

  • Trimarchi JM, Lees JA (2002) Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 3: 11–20.

    Article  PubMed  CAS  Google Scholar 

  • Tsantoulis PK, Gorgoulis VG (2005) Involvement of E2F transcription factor family in cancer. Eur J Cancer 41: 2403–2414.

    Article  PubMed  CAS  Google Scholar 

  • Tyagi S, Chabes AL, Wysocka J, et al. (2007) E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Mol Cell 27: 107–119.

    Article  PubMed  CAS  Google Scholar 

  • Urist M, Tanaka T, Poyurovsky MV, et al. (2004) p73 induction after DNA damage is regulated by checkpoint kinases Chk1 and Chk2. Genes Dev 18: 3041–3054.

    Article  PubMed  CAS  Google Scholar 

  • van de Peppel J, Kettelarij N, van Bakel H, et al. (2005) Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets. Mol Cell 19: 511–522.

    Article  PubMed  CAS  Google Scholar 

  • van den Heuvel S, Dyson NJ (2008) Conserved functions of the pRB and E2F families. Nat Rev Mol Cell Biol 9: 713–724.

    Article  PubMed  CAS  Google Scholar 

  • Vandel L, Kouzarides T (1999) Residues phosphorylated by TFIIH are required for E2F-1 degradation during S-phase. EMBO J 18: 4280–4291.

    Article  PubMed  CAS  Google Scholar 

  • Vassilev LT (2007) MDM2 inhibitors for cancer therapy. Trends Mol Med 13: 23–31.

    Article  PubMed  CAS  Google Scholar 

  • Verona R, Moberg K, Estes S, et al. (1997) E2F activity is regulated by cell cycle-dependent changes in subcellular localization. Mol Cell Biol 17: 7268–7282.

    PubMed  CAS  Google Scholar 

  • Vigo E, Muller H, Prosperini E, et al. (1999) CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase. Mol Cell Biol 19: 6379–6395.

    PubMed  CAS  Google Scholar 

  • Vincent O, Kuchin S, Hong SP, et al. (2001) Interaction of the Srb10 kinase with Sip4, a transcriptional activator of gluconeogenic genes in Saccharomyces cerevisiae. Mol Cell Biol 21: 5790–5796.

    Article  PubMed  CAS  Google Scholar 

  • Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81: 323–330.

    Article  PubMed  CAS  Google Scholar 

  • Wilson AC (2007) Setting the stage for S phase. Mol Cell 27: 176–177.

    Article  PubMed  CAS  Google Scholar 

  • Woychik NA, Hampsey M (2002) The RNA polymerase II machinery: structure illuminates function. Cell 108: 453–463.

    Article  PubMed  CAS  Google Scholar 

  • Wysocka J, Myers MP, Laherty CD, et al. (2003) Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes Dev 17: 896–911.

    Article  PubMed  CAS  Google Scholar 

  • Xu M, Sheppard KA, Peng CY, et al. (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 

  • Yang S, Jeung HC, Jeong HJ, et al. (2007) Identification of genes with correlated patterns of variations in DNA copy number and gene expression level in gastric cancer. Genomics 89: 451–459.

    Article  PubMed  CAS  Google Scholar 

  • Yudkovsky N, Ranish JA, Hahn S (2000) A transcription reinitiation intermediate that is stabilized by activator. Nature 408: 225–229.

    Article  PubMed  CAS  Google Scholar 

  • Zheng N, Fraenkel E, Pabo CO, et al. (1999) Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP. Genes Dev 13: 666–674.

    Article  PubMed  CAS  Google Scholar 

  • Zhu L (2005) Tumour suppressor retinoblastoma protein Rb: a transcriptional regulator. Eur J Cancer 41: 2415–2427.

    Article  PubMed  CAS  Google Scholar 

  • Zhu W, Giangrande PH, Nevins JR (2004) E2Fs link the control of G1/S and G2/M transcription. EMBO J 23: 4615–4626.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Drs. Erick Morris, Gerold Schubiger, and Fajun Yang for critical comments on this review. J.Y.J. is supported by a post-doctoral fellowship from the MGH Fund for Medical Discovery. This work was supported by a grant from the NIH (RO1 GM53203). N.J.D. is the MGH Saltonstall Foundation Scholar.

Author information

Authors and Affiliations

  1. Department of Pathology, Harvard Medical School, Massachusetts General Hospital Cancer Center, Charlestown, MA, 02129, USA

    Jun-Yuan Ji & Nicholas J. Dyson

  2. Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, TX, 77843, USA

    Jun-Yuan Ji

Authors
  1. Jun-Yuan Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicholas J. Dyson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun-Yuan Ji .

Editor information

Editors and Affiliations

  1. Dept. Medicine, Fox Chase Cancer Center, Cottman Ave. 333, Philadelphia, 19111-2497, Pennsylvania, USA

    Greg H. Enders

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Ji, JY., Dyson, N.J. (2010). Interplay Between Cyclin-Dependent Kinases and E2F-Dependent Transcription. In: Enders, G. (eds) Cell Cycle Deregulation in Cancer. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1770-6_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-1770-6_2

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-1769-0

  • Online ISBN: 978-1-4419-1770-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation