Distinct Roles of the Pocket Proteins in the Control of Cell Cycle

Chapter
First Online:

Abstract

The retinoblastoma (Rb) family of pocket proteins (pRb/p105 – the first tumor suppressor gene cloned in humans, p107 and p130) are critical mediators of cell cycle progression and are involved in transcription repression and cellular growth and differentiation. The Rb pocket proteins interact with different E2F family factors and can inhibit E2F-responsive promoters, interfering with progression of cell cycle, gene transcription, initiation of apoptotic process and cell differentiation. The activity of pRb and p130 may be involved in cellular response to DNA damage events, by influencing the transcription of factors involved in DNA repair pathways. In particular, Rb loss and target gene deregulation impacts the repair of UV-induced pyrimidine-pyrimidone photoproducts (6–4 PP) by regulating the expression of several DNA damage factors involved in the repair processes, including proliferating cell nuclear antigen (pCNA). Here we integrate and discuss recent evidence on the role of Rbs on the cell cycle engine, and how a new picture of Rb pathogenesis and progression is being shaped.

Keywords

Proliferate Cell Nuclear Antigen Cell Cycle Checkpoint Werner Syndrome Pocket Protein Pocket Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

We are grateful to Marco Cassone for critical reading of the manuscript, helpful discussions and encouragement. P.V. acknowledges the postdoctoral fellowship at Jefferson University, PA. This work was partially supported by grants from NIH, WV-INBRE, and MU-CDDC to P.P.C.

References

  1. Alonso MM, Fueyo J, Yung WK, Gomez-Manzano C (2006) E2F1 and telomerase: alliance in the dark side. Cell Cycle 5:930–5PubMedGoogle Scholar
  2. Alonso MM, Alemany R, Fueyo J, Gomez-Manzano C (2008) E2F1 in gliomas: a paradigm of oncogene addiction. Cancer Lett 263:157–63PubMedGoogle Scholar
  3. Bartek J, Lukas J (2001) Pathways governing G1/S transition and their response to DNA damage. FEBS Lett 490:117–22PubMedGoogle Scholar
  4. Bosco EE, Mayhew CN, Hennigan RF, Sage J, Jacks T, Knudsen ES (2004) RB signaling prevents replication-dependent DNA double-strand breaks following genotoxic insult. Nucleic Acids Res 32(1):25–34PubMedGoogle Scholar
  5. Bosco EE, Knudsen ES (2005) Differential role of RB in response to UV and IR damage. Nucleic Acids Res 33:1581–92PubMedGoogle Scholar
  6. Bosco EE, Wang Y, Xu H, Zilfou JT, Knudsen KE, Aronow BJ, Lowe SW, Knudsen ES (2007) The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J Clin Invest 117:218–28PubMedGoogle Scholar
  7. Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T (1998) Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391:597–601PubMedGoogle Scholar
  8. Cavenee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL, Murphree AL, Strong LC, White RL (1983) Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305:779–84PubMedGoogle Scholar
  9. Chang BD, Swift ME, Shen M, Fang J, Broude EV, Roninson IB (2002) Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent. Proc Natl Acad Sci USA 99:389–94PubMedGoogle Scholar
  10. Chen G, Guy CT, Chen HW, Hu N, Lee EY, Lee WH (1996) Molecular cloning and developmental expression of mouse p130, a member of the retinoblastoma gene family. J Biol Chem 271:9567–9572PubMedGoogle Scholar
  11. Chen CR, Kang Y, Siegel PM, Massagué J (2002) E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression. Cell 110:19–32PubMedGoogle Scholar
  12. Clarke AR, Maandag ER, van Roon M, van der Lugt NM, van der Valk M, Hooper ML, Berns A, te Riele H (1992) Requirement for a functional Rb-1 gene in murine development. Nature 359:328–30PubMedGoogle Scholar
  13. Classon M, Harlow E (2002) The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer 2:910–7PubMedGoogle Scholar
  14. Claudio PP, Howard CM, Baldi A, De Luca A, Fu Y, Condorelli G, Sun Y, Colburn N, Calabretta B, Giordano A (1994) p130/pRb2 has growth suppressive properties similar to yet distinctive from those of retinoblastoma family members pRb and p107. Cancer Res 54:5556–60PubMedGoogle Scholar
  15. 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 56:2003–2008PubMedGoogle Scholar
  16. Claudio PP, Tonini T, Giordano A (2002) The retinoblastoma family: twins or distant cousins? Genome Biol 3:reviews3012Google Scholar
  17. 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 10:1633–44PubMedGoogle Scholar
  18. Dahiya A, Wong S, Gonzalo S, Gavin M, Dean DC (2001) Linking the Rb and polycomb pathways. Mol Cell 8:557–69PubMedGoogle Scholar
  19. Dannenberg JH, van Rossum A, Schuijff L, te Riele H (2000) Ablation of the retinoblastoma gene family deregulates G(1) control causing immortalization and increased cell turnover under growth-restricting conditions. Genes Dev 14:3051–64PubMedGoogle Scholar
  20. Daria D, Filippi MD, Knudsen ES, Faccio R, Li Z, Kalfa T, Geiger H (2008) The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress. Blood 111:1894–902PubMedGoogle Scholar
  21. Datta PK, Raychaudhuri P, Bagchi S (1995) Association of p107 with Sp1: genetically separable regions of p107 are involved in regulation of E2F- and Sp1-dependent transcription. Mol Cell Biol 15:5444–5452PubMedGoogle Scholar
  22. David-Pfeuty T (2006) The flexible evolutionary anchorage-dependent Pardee’s restriction point of mammalian cells: how its deregulation may lead to cancer. Biochim Biophys Acta 1765:38–66PubMedGoogle Scholar
  23. De Luca A, MacLachlan TK, Bagella L, Dean C, Howard CM, Claudio PP, Baldi A, Khalili K, Giordano A (1997) A unique domain of pRb2/p130 acts as an inhibitor of Cdk2 kinase activity. J Biol Chem 272:20971–4PubMedGoogle Scholar
  24. Demogines A, Wong A, Aquadro C, Alani E (2008) Incompatibilities involving yeast mismatch repair genes: a role for genetic modifiers and implications for disease penetrance and variation in genomic mutation rates. PLoS Genet 4:e1000103PubMedGoogle Scholar
  25. Dimova DK, Dyson NJ (2005) The E2F transcriptional network: old acquaintances with new faces. Oncogene 24:2810–26PubMedGoogle Scholar
  26. Downs JA, Lowndes NF, Jackson SP (2000) A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature 408:1001–4PubMedGoogle Scholar
  27. Du W, Pogoriler J (2006) Retinoblastoma family genes. Oncogene 25:5190–200PubMedGoogle Scholar
  28. Du W, Vidal M, Xie JE, Dyson N (1996) RBF, a novel RB-related gene that regulates E2F activity and interacts with cyclin E in Drosophila. Genes Dev 10:1206–1218PubMedGoogle Scholar
  29. Dyson N (1998) The regulation of E2F by pRB-family proteins. Genes Dev 12:2245–62PubMedGoogle Scholar
  30. Faha B, Ewen ME, Tsai LH, Livingston DM, Harlow E (1992) Interaction between human cyclin A and adenovirus E1A-associated p107 protein. Science 255:87–90PubMedGoogle Scholar
  31. Foijer F, te Riele H (2006) Check, double check: the G2 barrier to cancer. Cell Cycle 5:831–6PubMedGoogle Scholar
  32. Genovese C, Trani D, Caputi M, Claudio PP (2006) Cell cycle control and beyond: emerging roles for the retinoblastoma gene family. Oncogene 25:5201–9PubMedGoogle Scholar
  33. 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 8:2665–79PubMedGoogle Scholar
  34. Gomez-Manzano C, Yung WK, Alemany R, Fueyo J (2004) Genetically modified adenoviruses against gliomas: from bench to bedside. Neurology 63:418–426PubMedGoogle Scholar
  35. Grillari J, Katinger H, Voglauer R (2007) Contributions of DNA interstrand cross-links to aging of cells and organisms. Nucleic Acids Res 35:7566–76PubMedGoogle Scholar
  36. Hallstrom TC, Nevins JR (2003) Specificity in the activation and control of transcription factor E2F-dependent apoptosis. Proc Natl Acad Sci USA 100:10848–53PubMedGoogle Scholar
  37. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70PubMedGoogle Scholar
  38. Hannon GJ, Demetrick D, Beach D (1993) Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins. Genes Dev 7:2378–2391PubMedGoogle Scholar
  39. Hartwell LH, Kastan MB (1994) Cell cycle control and cancer. Science 266:1821–8PubMedGoogle Scholar
  40. Horowitz JM, Park SH, Bogenmann E, Cheng JC, Yandell DW, Kaye FJ, Minna JD, Dryja TP, Weinberg RA (1990) Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells. Proc Natl Acad Sci USA 87:2775–9PubMedGoogle Scholar
  41. Hoskins EE, Gunawardena RW, Habash KB, Wise-Draper TM, Jansen M, Knudsen ES, Wells SI (2008) Coordinate regulation of Fanconi anemia gene expression occurs through the Rb/E2 pathway. Oncogene 27(35):4798–4808PubMedGoogle Scholar
  42. Howard CM, Claudio PP, De Luca A, Stiegler P, Jori FP, Safdar NM, Caputi M, Khalili K, Giordano A (2000) Inducible pRb2/p130 expression and growth-suppressive mechanisms: evidence of a pRb2/p130, p27Kip1, and cyclin E negative feedback regulatory loop. Cancer Res 60:2737–2744PubMedGoogle Scholar
  43. Howard CM, Claudio PP, Gallia GL, Gordon J, Giordano GG, Hauck WW, Khalili K, Giordano A (1998) Retinoblastoma-related protein pRb2/p130 and suppression of tumor growth in vivo. J Natl Cancer Inst 90:1451–60PubMedGoogle Scholar
  44. Hsieh JK, Chan FS, O’Connor DJ, Mittnacht S, Zhong S, Lu X (1999) RB regulates the stability and the apoptotic function of p53 via MDM2. Mol Cell 3:181–93PubMedGoogle Scholar
  45. Hunter N, Börner GV, Lichten M, Kleckner N (2001) Gamma-H2AX illuminates meiosis. Nat Genet 27:236–8PubMedGoogle Scholar
  46. Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA (1992) Effects of an Rb mutation in the mouse. Nature 359:295–300PubMedGoogle Scholar
  47. Jori FP, Melone MA, Napolitano MA, Cipollaro M, Cascino A, Giordano A, Galderisi U (2005) RB and RB2/p130 genes demonstrate both specific and overlapping functions during the early steps of in vitro neural differentiation of marrow stromal stem cells. Cell Death Differ 12:65–77PubMedGoogle Scholar
  48. Jori FP, Galderisi U, Napolitano MA, Cipollaro M, Cascino A, Giordano A, Melone MA (2007) RB and RB2/P130 genes cooperate with extrinsic signals to promote differentiation of rat neural stem cells. Mol Cell Neurosci 34:299–309PubMedGoogle Scholar
  49. Kadam S, Emerson BM (2003) Transcriptional specificity of human SWI/SNF BRG1 and BRM chromatin remodeling complexes. Mol Cell 11:377–89PubMedGoogle Scholar
  50. Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27:247–54PubMedGoogle Scholar
  51. Knudsen KE, Booth D, Naderi S, Sever-Chroneos Z, Fribourg AF, Hunton IC, Feramisco JR, Wang JY, Knudsen ES (2000) RB-dependent S-phase response to DNA damage. Mol Cell Biol 20:7751–63PubMedGoogle Scholar
  52. Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–3PubMedGoogle Scholar
  53. Knudson AG Jr, Hethcote HW, Brown BW (1975) Mutation and childhood cancer: a probabilistic model for the incidence of retinoblastoma. Proc Natl Acad Sci USA 72:5116–20PubMedGoogle Scholar
  54. Knudson AG (1993) Antioncogenes and human cancer. Proc Natl Acad Sci USA 90:10914–21PubMedGoogle Scholar
  55. Lara MF, Santos M, Ruiz S, Segrelles C, Moral M, Martínez-Cruz AB, Hernández P, ­Martínez-Palacio J, Lorz C, García-Escudero R, Paramio JM (2008) p107 acts as a tumor suppressor in pRb-deficient epidermis. Mol Carcinog 47:105–13PubMedGoogle Scholar
  56. Lee EY, To H, Shew JY, Bookstein R, Scully P, Lee WH (1988) Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science 241:218–21PubMedGoogle Scholar
  57. Lee EY, Chang CY, Hu N, Wang YC, Lai CC, Herrup K, Lee WH, Bradley A (1992) Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359:288–94PubMedGoogle Scholar
  58. Lee JO, Russo AA, Pavletich NP (1998) Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7. Nature 391:859–865PubMedGoogle Scholar
  59. Lee WH, Bookstein R, Hong F, Young LJ, Shew JY, Lee EY (1987) Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 235:1394–1399PubMedGoogle Scholar
  60. Lees E, Faha B, Dulic V, Reed SI, Harlow E (1992) Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner. Genes Dev 6:1874–1885PubMedGoogle Scholar
  61. Li Y, Graham C, Lacy S, Duncan AM, Whyte P (1993) 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 7:2366–2377PubMedGoogle Scholar
  62. Li J, Ran C, Li E, Gordon F, Comstock G, Siddiqui H, Cleghorn W, Chen HZ, Kornacker K, Liu CG, Pandit SK, Khanizadeh M, Weinstein M, Leone G, de Bruin A (2008) Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development. Dev Cell 14:62–75PubMedGoogle Scholar
  63. Lipinski MM, Jacks T (1999) The retinoblastoma gene family in differentiation and development. Oncogene 18:7873–82PubMedGoogle Scholar
  64. Liu DX, Nath N, Chellappan SP, Greene LA (2005) Regulation of neuron survival and death by p130 and associated chromatin modifiers. Genes Dev 19:719–32PubMedGoogle Scholar
  65. Llorente B, Smith CE, Symington LS (2008) Break-induced replication: what is it and what is it for? Cell Cycle 7:859–64PubMedGoogle Scholar
  66. Luo RX, Postigo AA, Dean DC (1998) Rb interacts with histone deacetylase to repress transcription. Cell 92:463–73PubMedGoogle Scholar
  67. Macpherson D (2008) Insights from mouse models into human retinoblastoma. Cell Div 3:9PubMedGoogle Scholar
  68. MacPherson D, Dyer MA (2007) Retinoblastoma: from the two-hit hypothesis to targeted chemotherapy. Cancer Res 67:7547–50PubMedGoogle Scholar
  69. Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D, Harel-Bellan A (1998) Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature 391:601–5PubMedGoogle Scholar
  70. Markey MP, Angus SP, Strobeck MW, Williams SL, Gunawardena RW, Aronow BJ, Knudsen ES (2002) Unbiased analysis of RB-mediated transcriptional repression identifies novel targets and distinctions from E2F action. Cancer Res 62:6587–97PubMedGoogle Scholar
  71. Morgenbesser SD, Williams BO, Jacks T, DePinho RA (1994) p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens. Nature 371:72–4PubMedGoogle Scholar
  72. Nemajerova A, Talos F, Moll UM, Petrenko O (2008) Rb function is required for E1A-induced S-phase checkpoint activation. Cell Death Differ 15(9):1440–1449PubMedGoogle Scholar
  73. Nevins JR (1992) E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 258:424–429PubMedGoogle Scholar
  74. Niculescu AB 3rd, Chen X, Smeets M, Hengst L, Prives C, Reed SI (1998) Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication. Mol Cell Biol 18:629–43PubMedGoogle Scholar
  75. Pardee AB (1974) A restriction point for control of normal animal cell proliferation. Proc Natl Acad Sci USA 71:1286–90PubMedGoogle Scholar
  76. Pertile P, Baldi A, De Luca A, Bagella L, Virgilio L, Pisano MM, Giordano A (1995) Molecular cloning, expression, and developmental characterization of the murine retinoblastoma-related gene Rb2/p130. Cell Growth Differ 6:1659–1664PubMedGoogle Scholar
  77. Petrini JH, Stracker TH (2003) The cellular response to DNA double-strand breaks: defining the sensors and mediators. Trends Cell Biol 13:458–62PubMedGoogle Scholar
  78. Pickering MT, Kowalik TF (2006) Rb inactivation leads to E2F1-mediated DNA double-strand break accumulation. Oncogene 25:746–55PubMedGoogle Scholar
  79. 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 G(2)/M checkpoints. Genes Dev 16:245–56PubMedGoogle Scholar
  80. Ross JF, Näär A, Cam H, Gregory R, Dynlacht BD (2001) Active repression and E2F inhibition by pRB are biochemically distinguishable. Genes Dev 15:392–7PubMedGoogle Scholar
  81. Ruiz S, Segrelles C, Bravo A, Santos M, Perez P, Leis H, Jorcano JL, Paramio JM (2003) Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130. Development 130:2341–53PubMedGoogle Scholar
  82. Ruiz S, Santos M, Segrelles C, Leis H, Jorcano JL, Berns A, Paramio JM, Vooijs M (2004) Unique and overlapping functions of pRb and p107 in the control of proliferation and differentiation in epidermis. Development 131:2737–48PubMedGoogle Scholar
  83. Sabelli PA, Dante RA, Leiva-Neto JT, Jung R, Gordon-Kamm WJ, Larkins BA (2005) RBR3, a member of the retinoblastoma-related family from maize, is regulated by the RBR1/E2F pathway. Proc Natl Acad Sci USA 102:13005–12PubMedGoogle Scholar
  84. Sabelli PA, Larkins BA (2006) Grasses like mammals? Redundancy and compensatory regulation within the retinoblastoma protein family. Cell Cycle 5:352–5PubMedGoogle Scholar
  85. Sage J, Mulligan GJ, Attardi LD, Miller A, Chen S, Williams B, Theodorou E, Jacks T (2000) Targeted disruption of the three Rb-related genes leads to loss of G(1) control and immortalization. Genes Dev 14:3037–50PubMedGoogle Scholar
  86. Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen 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 92:2403–7PubMedGoogle Scholar
  87. Sghaier H, Ghedira K, Benkahla A, Barkallah I (2008) Basal DNA repair machinery is subject to positive selection in ionizing-radiation-resistant bacteria. BMC Genomics 9:297PubMedGoogle Scholar
  88. Sherr CJ (1996) Cancer cell cycles. Science 274:1672–7PubMedGoogle Scholar
  89. Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13:1501–12PubMedGoogle Scholar
  90. Spike BT, Dirlam A, Dibling BC, Marvin J, Williams BO, Jacks T, Macleod KF (2004) The Rb tumor suppressor is required for stress erythropoiesis. EMBO J 23:4319–29PubMedGoogle Scholar
  91. Stengel KR, Dean JL, Seeley SL, Mayhew CN, Knudsen ES (2008) RB status governs differential sensitivity to cytotoxic and molecularly-targeted therapeutic agents. Cell Cycle 7:1095–103PubMedGoogle Scholar
  92. Temple S, Raff MC (1986) Clonal analysis of oligodendrocyte development in culture: evidence for a developmental clock that counts cell divisions. Cell 44:773–9PubMedGoogle Scholar
  93. Tonini T, Hillson C, Claudio PP (2002) Interview with the retinoblastoma family members: do they help each other? J Cell Physiol 192:138–50PubMedGoogle Scholar
  94. Umen JG, Goodenough UW (2001) Control of cell division by a retinoblastoma protein homolog in Chlamydomonas. Genes Dev 15:1652–1661PubMedGoogle Scholar
  95. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303:844–848PubMedGoogle Scholar
  96. Vidal A, Carneiro C, Zalvide JB (2007) Of mice without pockets: mouse models to study the function of Rb family proteins. Front Biosci 12:4483–96PubMedGoogle Scholar
  97. Wang JY, Naderi S, Chen TT (2001) Role of retinoblastoma tumor suppressor protein in DNA damage response. Acta Oncol 40:689–95PubMedGoogle Scholar
  98. Wang Q, Li YC, Wang J, Kong J, Qi Y, Quigg RJ, Li X (2008) miR-17–92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc Natl Acad Sci USA 105:2889–94PubMedGoogle Scholar
  99. Weber T, Corbett MK, Chow LM, Valentine MB, Baker SJ, Zuo J (2008) Rapid cell-cycle reentry and cell death after acute inactivation of the retinoblastoma gene product in postnatal cochlear hair cells. Proc Natl Acad Sci USA 105:781–5PubMedGoogle Scholar
  100. Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81:323–30PubMedGoogle Scholar
  101. White AE, Livanos EM, Tlsty TD (1994) Differential disruption of genomic integrity and cell cycle regulation in normal human fibroblasts by the HPV oncoproteins. Genes Dev 8:666–77PubMedGoogle Scholar
  102. Wikenheiser-Brokamp KA (2006) Retinoblastoma family proteins: insights gained through genetic manipulation of mice. Cell Mol Life Sci 63:767–80PubMedGoogle Scholar
  103. Woo MS, Sánchez I, Dynlacht BD (1997) p130 and p107 use a conserved domain to inhibit cellular cyclin-dependent kinase activity. Mol Cell Biol 17:3566–79PubMedGoogle Scholar
  104. Yang J, Yu Y, Hamrick HE, Duerksen-Hughes PJ (2003) ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. Carcinogenesis 24:1571–80PubMedGoogle Scholar
  105. Yeung RS, Bell DW, Testa JR, Mayol X, Baldi A, Grana X, Klinga-Levan K, Knudson AG, Giordano A (1993) The retinoblastoma-related gene, RB2, maps to human chromosome 16q12 and rat chromosome 19. Oncogene 8:3465–3468PubMedGoogle Scholar
  106. Zagorski WA, Knudsen ES, Reed MF (2007) Retinoblastoma deficiency increases chemosensitivity in lung cancer. Cancer Res 67:8264–73PubMedGoogle Scholar
  107. Zalmas LP, Zhao X, Graham AL, Fisher R, Reilly C, Coutts AS, La Thangue NB (2008) DNA-damage response control of E2F7 and E2F8. EMBO Rep 9:252–9PubMedGoogle Scholar
  108. Zhang HS, Gavin M, Dahiya A, Postigo AA, Ma D, Luo RX, Harbour JW, Dean DC (2000) Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF. Cell 101:79–89PubMedGoogle Scholar
  109. Zhu L, van den Heuvel S, Helin K, Fattaey A, Ewen M, Livingston D, Dyson N, Harlow E (1993) Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. Genes Dev 7:1111–1125PubMedGoogle Scholar
  110. Zhu L, Enders G, Lees JA, Beijersbergen RL, Bernards R, Harlow E (1995a) The pRB-related protein p107 contains two growth suppression domains: independent interactions with E2F and cyclin/cdk complexes. EMBO J 14:1904–1913PubMedGoogle Scholar
  111. Zhu L, Harlow E, Dynlacht BD (1995b) p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F. Genes Dev 9:1740–1752PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Department of Cancer BiologyThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Department of Biochemistry and Microbiology Joan C. Edwards School of MedicineMarshall UniversityHuntingtonUSA

Personalised recommendations