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Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Oncogene volume 25, pages 5277–5285 (2006)Cite this article

Abstract

RB, the most investigated tumor suppressor gene, is the founder of the RB family of growth/tumor suppressors, which comprises also p107 (RBL1) and Rb2/p130 (RBL2). The protein products of these genes, pRb, p107 and pRb2/p130, respectively, are also known as ‘pocket proteins’, because they share a ‘pocket’ domain responsible for most of the functional interactions characterizing the activity of this family of cellular factors. The interest in these genes and proteins springs essentially from their ability to regulate negatively cell cycle processes and for their ability to slow down or abrogate neoplastic growth. The pocket domain of the RB family proteins is dramatically hampered in its functions by the interference of a number of proteins produced by the small DNA viruses. In the last two decades, the ‘viral hypothesis’ of cancer has received a considerable renewed impulse from the notion that small DNA viruses, such as Adenovirus, Human papillomavirus (HPV) and Polyomavirus, produce factors that can physically interact with major cellular regulators and alter their function. These viral proteins (oncoproteins) act as multifaceted molecular devices that have evolved to perform very specific tasks. Owing to these features, viral oncoproteins have been widely employed as invaluable experimental tools for the identification of several key families of regulators, particularly of the cell cycle homeostasis. Adenovirus early-region 1A (E1A) is the most widely investigated small DNA tumor virus oncoprotein, but relevant interest in human oncology is raised by the E1A-related E7 protein from transforming HPV strains and by Polyomavirus oncoproteins, particularly large and small T antigens from Simian virus 40, JC virus and BK virus.

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References

  • Ach RA, Durfee T, Miller AB, Taranto P, Hanley-Bowdoin L, Zambryski PC et al. (1997). Mol Cell Biol 17: 5077–5086.

  • Ali SH, DeCaprio JA . (2001). Semin Cancer Biol 11: 15–23.

  • Antinore MJ, Birrer MJ, Patel D, Nader L, McCance DJ . (1996). EMBO J 15: 1950–1960.

  • Arany Z, Newsome D, Oldread E, Livingston DM, Eckner R . (1995). Nature 374: 81–84.

  • Arbeit JM, Howley PM, Hanahan D . (1996). Proc Natl Acad Sci USA 93: 2930–2935.

  • Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS, Kelly K . (1997). Cell 89: 1175–1184.

  • Avvakumov N, Kajon AE, Hoeben RC, Mymryk JS . (2004). Virology 329: 477–492.

  • Avvakumov N, Torchia J, Mymryk JS . (2003). Oncogene 22: 3833–3841.

  • Banks L, Edmonds C, Vousden KH . (1990). Oncogene 5: 1383–1389.

  • Barbanti-Brodano G, Sabbioni S, Martini F, Negrini M, Corallini A, Tognon M . (2004). Virology 318: 1–9.

  • Bartek J, Bartkova J, Lukas J . (1997). Exp Cell Res 237: 1–6.

  • Beijersbergen RL, Kerkhoven RM, Zhu L, Carlée L, Voorhoeve PM, Bernards R . (1994). Genes Dev 8: 2680–2690.

  • Ben Porath I, Weinberg RA . (2004). J Clin Invest 113: 8–13.

  • Ben Porath I, Weinberg RA . (2005). Int J Biochem Cell Biol 37: 961–976.

  • Berezutskaya E, Yu B, Morozov A, Raychaudhuri P, Bagchi S . (1997). Cell Growth Differ 8: 1277–1286.

  • Berger JR, Concha M . (1995). J Neurovirol 1: 5–18.

  • Berk AJ . (2005). Oncogene 24: 7673–7685.

  • Boffetta P . (2004). Oncogene 23: 6392–6403.

  • Bollag B, Chuke WF, Frisque RJ . (1989). J Virol 63: 863–872.

  • Bollag B, Prins C, Snyder EL, Frisque RJ . (2000). Virology 274: 165–178.

  • Boyer SN, Wazer DE, Band V . (1996). Cancer Res 56: 4620–4624.

  • Brehm A, Nielsen SJ, Miska EA, McCance DJ, Reid JL, Bannister AJ et al. (1999). EMBO J 18: 2449–2458.

  • Brokaw JL, Yee CL, Munger K . (1994). Virology 205: 603–607.

  • Caldeira S, De Villiers EM, Tommasino M . (2000). Oncogene 19: 821–826.

  • Campbell KS, Mullane KP, Aksoy IA, Stubdal H, Zalvide J, Pipas JM et al. (1997). Genes Dev 11: 1098–1110.

  • Cao L, Faha B, Dembski M, Tsai LH, Harlow E, Dyson N . (1992). Nature 355: 176–179.

  • Carbone M . (2000). J Cell Biochem 76: 189–193.

  • Carbone M, Pass HI, Rizzo P, Marinetti M, Di Muzio M, Mew DJ et al. (1994). Oncogene 9: 1781–1790.

  • Carbone M, Rizzo P, Pass HI . (1997). Oncogene 15: 1877–1888.

  • Cenciarelli C, De Santa F, Puri PL, Mattei E, Ricci L, Bucci F et al. (1999). Mol Cell Biol 19: 5203–5217.

  • Chan HM, Krstic-Demonacos M, Smith L, Demonacos C, La Thangue NB . (2001). Nat Cell Biol 3: 667–674.

  • Chan HM, Narita M, Lowe SW, Livingston DM . (2005). Genes Dev 19: 196–201.

  • Christensen JB, Imperiale MJ . (1995). J Virol 69: 3945–3948.

  • Ciccolini F, Di Pasquale G, Carlotti F, Crawford L, Tommasino M . (1994). Oncogene 9: 2633–2638.

  • Classon M, Dyson N . (2001). Exp Cell Res 264: 135–147.

  • Claudio PP, Howard CM, Baldi A, De Luca A, Fu Y, Condorelli G et al. (1994). Cancer Res 54: 5556–5560.

  • Cole CN . (1996). Polyomaviridae: The viruses and their replication. In: Knipe PM (ed). Fundamental Virology. Lippincott, Raven: Philadelphia, pp 917–945.

    Google Scholar 

  • Croul S, Otte J, Khalili K . (2003). J Neurovirol 9: 173–182.

  • Dahiya A, Gavin MR, Luo RX, Dean DC . (2000). Mol Cell Biol 20: 6799–6805.

  • Dang-Tan T, Mahmud SM, Puntoni R, Franco EL . (2004). Oncogene 23: 6535–6540.

  • Datto MB, Hu PP, Kowalik TF, Yingling J, Wang XF . (1997). Mol Cell Biol 17: 2030–2037.

  • Davies R, Hicks R, Crook T, Morris J, Vousden K . (1993). J Virol 67: 2521–2528.

  • De Stanchina E, McCurrach ME, Zindy F, Shieh SY, Ferbeyre G, Samuelson AV et al. (1998). Genes Dev 12: 2434–2442.

  • De Villiers EM, Fauquet C, Broker TR, Bernard HU, zur HH . (2004). Virology 324: 17–27.

  • Demers GW, Foster SA, Halbert CL, Galloway DA . (1994). Proc Natl Acad Sci USA 91: 4382–4386.

  • Dyson N, Buchkovich K, Whyte P, Harlow E . (1989a). Cell 58: 249–255.

  • Dyson N, Guida P, McCall C, Harlow E . (1992). J Virol 66: 4606–4611.

  • Dyson N, Howley PM, Munger K, Harlow E . (1989b). Science 243: 934–937.

  • Eckner R, Yao TP, Oldread E, Livingston DM . (1996). Genes Dev 10: 2478–2490.

  • Engels EA . (2005). Expert Rev Vaccines 4: 197–206.

  • Ewen ME . (1994). Cancer Metast Rev 13: 45–66.

  • Ewen ME, Xing YG, Lawrence JB, Livingston DM . (1991). Cell 66: 1155–1164.

  • Fattaey AR, Harlow E, Helin K . (1993). Mol Cell Biol 13: 7267–7277.

  • Fioriti D, Videtta M, Mischitelli M, Degener AM, Russo G, Giordano A et al. (2005). J Cell Physiol 204: 402–406.

  • Flores ER, Allen-Hoffmann BL, Lee D, Lambert PF . (2000). J Virol 74: 6622–6631.

  • Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM et al. (1986). Nature 323: 643–646.

  • Frisch SM, Mymryk JS . (2002). Nat Rev Mol Cell Biol 3: 441–452.

  • Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V et al. (2001). Cell 106: 297–307.

  • Gage JR, Meyers C, Wettstein FO . (1990). J Virol 64: 723–730.

  • Ghosh MK, Harter ML . (2003). Mol Cell 12: 255–260.

  • Giordano A, Whyte P, Harlow E, Franza Jr BR, Beach D, Draetta G . (1989). Cell 58: 981–990.

  • Gonzalez SL, Stremlau M, He X, Basile JR, Munger K . (2001). J Virol 75: 7583–7591.

  • Goodrich DW, Wang NP, Qian YW, Lee EY, Lee WH . (1991). Cell 67: 293–302.

  • Haggerty S, Walker DL, Frisque RJ . (1989). J Virol 63: 2180–2190.

  • Hannon GJ, Demetrick D, Beach D . (1993). Genes Dev 7: 2378–2391.

  • Harlow E, Whyte P, Franza Jr BR, Schley C . (1986). Mol Cell Biol 6: 1579–1589.

  • Harris KF, Chang E, Christensen JB, Imperiale MJ . (1998a). Dev Biol Stand 94: 81–91.

  • Harris KF, Christensen JB, Imperiale MJ . (1996). J Virol 70: 2378–2386.

  • Harris KF, Christensen JB, Radany EH, Imperiale MJ . (1998b). Mol Cell Biol 18: 1746–1756.

  • Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT . (1989). EMBO J 8: 3905–3910.

  • Helin K, Harlow E, Fattaey A . (1993). Mol Cell Biol 13: 6501–6508.

  • Helin K, Lees JA, Vidal M, Dyson N, Harlow E, Fattaey A . (1992). Cell 70: 337–350.

  • Helt AM, Galloway DA . (2001). J Virol 75: 6737–6747.

  • Helt AM, Galloway DA . (2003). Carcinogenesis 24: 159–169.

  • Herrmann CH, Su LK, Harlow E . (1991). J Virol 65: 5848–5859.

  • Herwig S, Strauss M . (1997). Eur J Biochem 246: 581–601.

  • Hijmans EM, Voorhoeve PM, Beijersbergen RL, Van ‘t Veer LJ, Bernards R . (1995). Mol Cell Biol 15: 3082–3089.

  • Hu G, Liu W, Hanania EG, Fu S, Wang T, Deisseroth AB . (1995). Cancer Gene Ther 2: 19–32.

  • Hurford Jr RK, Cobrinik D, Lee MH, Dyson N . (1997). Genes Dev 11: 1447–1463.

  • Ikeda MA, Nevins JR . (1993). Mol Cell Biol 13: 7029–7035.

  • Iyer NG, Ozdag H, Caldas C . (2004). Oncogene 23: 4225–4231.

  • Jasani B, Cristaudo A, Emri SA, Gazdar AF, Gibbs A, Krynska B et al. (2001). Semin Cancer Biol 11: 49–61.

  • Jewers RJ, Hildebrandt P, Ludlow JW, Kell B, McCance DJ . (1992). J Virol 66: 1329–1335.

  • Jones DL, Thompson DA, Münger K . (1997). Virology 239: 97–107.

  • Kaelin Jr WG . (1999). BioEssays 21: 950–958.

  • Kapic A, Helmbold H, Reimer R, Klotzsche O, Deppert W, Bohn W . (2006). Cell Death Differ 13: 324–334.

  • Kelley WL, Georgopoulos C . (1997). Proc Natl Acad Sci USA 94: 3679–3684.

  • Khalili K, Del Valle L, Otte J, Weaver M, Gordon J . (2003). Oncogene 22: 5181–5191.

  • Kim HY, Ahn BY, Cho Y . (2001). EMBO J 20: 295–304.

  • Klein G, Powers A, Croce C . (2002). Oncogene 21: 1141–1149.

  • Knudsen ES, Wang JY . (1998). Oncogene 16: 1655–1663.

  • Knudson AGJ . (1971). Proc Natl Acad Sci USA 68: 820–823.

  • Knudson AGJ . (1986). Annu Rev Genet 20: 231–251.

  • Kouzarides T . (1995). Semin Cancer Biol 6: 91–98.

  • Kreimer AR, Clifford GM, Boyle P, Franceschi S . (2005). Cancer Epidemiol Biomarkers Prev 14: 467–475.

  • Lavia P, Mileo AM, Giordano A, Paggi MG . (2003). Oncogene 22: 6508–6516.

  • Lee C, Chang JH, Lee HS, Cho Y . (2002). Genes Dev 16: 3199–3212.

  • Lee JO, Russo AA, Pavletich NP . (1998). Nature 391: 859–865.

  • Li Y, Graham C, Lacy S, Duncan AM, Whyte P . (1993). Genes Dev 7: 2366–2377.

  • Lill NL, Grossman SR, Ginsberg D, DeCaprio J, Livingston DM . (1997). Nature 387: 823–827.

  • Lin JY, DeCaprio JA . (2003). J Biol Chem 278: 46482–46487.

  • Liu H, Dibling B, Spike B, Dirlam A, Macleod K . (2004). Curr Opin Genet Dev 14: 55–64.

  • Lu XW, Horvitz HR . (1998). Cell 95: 981–991.

  • Magenta A, Cenciarelli C, De Santa F, Fuschi P, Martelli F, Caruso M et al. (2003). Mol Cell Biol 23: 2893–2906.

  • Mal A, Chattopadhyay D, Ghosh MK, Poon RYC, Hunter T, Harter ML . (2000). J Cell Biol 149: 281–292.

  • Mal A, Poon RYC, Howe PH, Toyoshima H, Hunter T, Harter ML . (1996). Nature 380: 262–265.

  • Martelli F, Cenciarelli C, Santarelli G, Polikar B, Felsani A, Caruso M . (1994). Oncogene 9: 3579–3590.

  • Mayol X, Graña X, Baldi A, Sang N, Hu Q, Giordano A . (1993). Oncogene 8: 2561–2566.

  • McCance DJ, Kopan R, Fuchs E, Laimins LA . (1988). Proc Natl Acad Sci USA 85: 7169–7173.

  • McIntyre MC, Frattini MG, Grossman SR, Laimins LA . (1993). J Virol 67: 3142–3150.

  • Missero C, Calautti E, Eckner R, Chin J, Tsai LH, Livingston DM et al. (1995). Proc Natl Acad Sci USA 92: 5451–5455.

  • Morris EJ, Dyson NJ . (2001). Adv Cancer Res 82: 1–54.

  • Mortimer Jr EA, Lepow ML, Gold E, Robbins FC, Burton GJ, Fraumeni Jr JF . (1981). N Engl J Med 305: 1517–1518.

  • Mossman BT, Gee JB . (1989). N Engl J Med 320: 1721–1730.

  • Müller H, Helin K . (2000). Biochim Biophys Acta Rev Cancer 1470: M1–M12.

  • Mulligan G, Jacks T . (1998). Trends Genet 14: 223–229.

  • Munger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M et al. (2004). J Virol 78: 11451–11460.

  • Munger K, Basile JR, Duensing S, Eichten A, Gonzalez SL, Grace M et al. (2001). Oncogene 20: 7888–7898.

  • Munger K, Phelps WC, Bubb V, Howley PM, Schlegel R . (1989a). J Virol 63: 4417–4421.

  • Munger K, Werness BA, Dyson N, Phelps WC, Harlow E, Howley PM . (1989b). EMBO J 8: 4099–4105.

  • Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV et al. (2003). N Engl J Med 348: 518–527.

  • Nguyen DX, Baglia LA, Huang SM, Baker CM, McCance DJ . (2004). EMBO J 23: 1609–1618.

  • Paggi MG, Baldi A, Bonetto F, Giordano A . (1996). J Cell Biochem 62: 418–430.

  • Paggi MG, Giordano A . (2001). Cancer Res 61: 4651–4654.

  • Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ . (2000). J Biol Chem 275: 6764–6769.

  • Patrick DR, Oliff A, Heimbrook DC . (1994). J Biol Chem 269: 6842–6850.

  • Pfister H . (2003). J Natl Cancer Inst Monogr 31: 52–56.

  • Phelps WC, Yee CL, Munger K, Howley PM . (1988). Cell 53: 539–547.

  • Pines J, Hunter T . (1990). Nature 346: 760–763.

  • Powell AJ, Darmon AJ, Gonos ES, Lam EWF, Peden KWC, Jat PS . (1999). Oncogene 18: 7343–7350.

  • Reinstein E, Scheffner M, Oren M, Ciechanover A, Schwartz A . (2000). Oncogene 19: 5944–5950.

  • Reiss K, Khalili K . (2003). Oncogene 22: 6517–6523.

  • Riley DJ, Lee EYHP, Lee W-H . (1994). Annu Rev Cell Biol 10: 1–29.

  • Rizzo P, Di Resta I, Powers A, Ratner H, Carbone M . (1999). Cancer Res 59: 6103–6108.

  • Sang N, Caro J, Giordano A . (2002). Front Biosci 7: D407–D413.

  • Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A et al. (1995). Proc Natl Acad Sci USA 92: 2403–2407.

  • Scheffner M, Whitaker NJ . (2003). Semin Cancer Biol 13: 59–67.

  • Schmitt A, Harry JB, Rapp B, Wettstein FO, Iftner T . (1994). J Virol 68: 7051–7059.

  • Shan B, Durfee T, Lee WH . (1996). Proc Natl Acad Sci USA 93: 679–684.

  • Shirodkar S, Ewen ME, DeCaprio JA, Morgan J, Livingston DM, Chittenden T . (1992). Cell 68: 157–166.

  • Sidle A, Palaty C, Dirks P, Wiggan O, Kiess M, Gill RM et al. (1996). Crit Rev Biochem Mol Biol 31: 237–271.

  • Singh M, Krajewski M, Mikolajka A, Holak TA . (2005). J Biol Chem 280: 37868–37876.

  • Somasundaram K, el-Deiry WS . (1997). Oncogene 14: 1047–1057.

  • Srinivasan A, McClellan AJ, Vartikar J, Marks I, Cantalupo P, Li Y et al. (1997). Mol Cell Biol 17: 4761–4773.

  • Starostik P, Chow KNB, Dean DC . (1996). Mol Cell Biol 16: 3606–3614.

  • Steegenga WT, van Laar T, Riteco N, Mandarino A, Shvarts A, van der Eb AJ et al. (1996). Mol Cell Biol 16: 2101–2109.

  • Stein RW, Corrigan M, Yaciuk P, Whelan J, Moran E . (1990). J Virol 64: 4421–4427.

  • Stevaux O, Dyson NJ . (2002). Curr Opin Cell Biol 14: 684–691.

  • Stiegler P, Kasten M, Giordano A . (1998). J Cell Biochem Suppl 30–31: 30–36.

  • Strickler HD, Rosenberg PS, Devesa SS, Hertel J, Fraumeni Jr JF, Goedert JJ . (1998). JAMA 279: 292–295.

  • Stubdal H, Zalvide J, Campbell KS, Schweitzer C, Roberts TM, DeCaprio JA . (1997). Mol Cell Biol 17: 4979–4990.

  • Stubdal H, Zalvide J, DeCaprio JA . (1996). J Virol 70: 2781–2788.

  • Sullivan CS, Tremblay JD, Fewell SW, Lewis JA, Brodsky JL, Pipas JM . (2000). Mol Cell Biol 20: 5749–5757.

  • Thomas DM, Yang HS, Alexander K, Hinds PW . (2003). Cancer Biol Ther 2: 124–130.

  • Tognon M, Corallini A, Martini F, Negrini M, Barbanti-Brodano G . (2003). Oncogene 22: 5192–5200.

  • Tommasino M, Crawford L . (1995). BioEssays 17: 509–518.

  • Trowbridge PW, Frisque RJ . (1995). J Neurovirol 1: 195–206.

  • Tweedale G . (2002). Nat Rev Cancer 2: 311–315.

  • Vogelstein B, Lane D, Levine AJ . (2000). Nature 408: 307–310.

  • Vousden KH, Jat PS . (1989). Oncogene 4: 153–158.

  • Wang JY, Del Valle L, Peruzzi F, Trojanek J, Giordano A, Khalili K et al. (2004). J Exp Clin Cancer Res 23: 373–383.

  • Weinberg RA . (1995). Cell 81: 323–330.

  • Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, Weinberg RA et al. (1988). Nature 334: 124–129.

  • Whyte P, Williamson NM, Harlow E . (1989). Cell 56: 67–75.

  • Xiao B, Spencer J, Clements A, Ali-Khan N, Mittnacht S, Broceno C et al. (2003). Proc Natl Acad Sci USA 100: 2363–2368.

  • Yuan WC, Condorelli G, Caruso M, Felsani A, Giordano A . (1996). J Biol Chem 271: 9009–9013.

  • Zalvide J, DeCaprio JA . (1995). Mol Cell Biol 15: 5800–5810.

  • Zalvide J, Stubdal H, DeCaprio JA . (1998). Mol Cell Biol 18: 1408–1415.

  • Zhang Y, Fan S, Meng Q, Ma Y, Katiyar P, Schlegel R et al. (2005). J Biol Chem 280: 33165–33177.

  • Zhu L, van den Heuvel S, Helin K, Fattaey A, Ewen ME, Livingston DM et al. (1993). Genes Dev 7: 1111–1125.

  • zur Hausen H . (1996). Biochim Biophys Acta 1288: F55–F78.

  • zur Hausen H . (2000). J Natl Cancer Inst 92: 690–698.

  • zur Hausen H . (2002). Nat Rev Cancer 2: 342–350.

  • Zwerschke W, Jansen-Durr P . (2000). Adv Cancer Res 78: 1–29.

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Acknowledgements

Research in our laboratories was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC) and Ministero della Salute grants to MGP, and by Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Project ‘Applicazione delle nuove conoscenze e tecnologie in oncologia’ grant to AF.

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  1. Istituto di Neurobiologia e Medicina Molecolare, CNR, Rome, Italy

    A Felsani

  2. Regina Elena Cancer Institute, Rome, Italy

    A M Mileo & M G Paggi

  3. Center of Biotechnology, Temple University, Philadelphia, PA, USA

    M G Paggi

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Felsani, A., Mileo, A. & Paggi, M. Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins. Oncogene 25, 5277–5285 (2006). https://doi.org/10.1038/sj.onc.1209621

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