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pRb: master of differentiation. Coupling irreversible cell cycle withdrawal with induction of muscle-specific transcription

Oncogene volume 25, pages 5244–5249 (2006)Cite this article

Abstract

The protein product of the retinoblastoma (RB) gene is necessary for the completion of the muscle differentiation program and for myogenic basic helix–loop–helix-dependent transcription. In fact, in addition to induction and maintenance of permanent cell cycle withdrawal through negative regulation of E2F-responsive genes involved in proliferation, pRb also plays a positive role in the activation of muscle-specific genes. In pRb−/− myocytes, the expression of late myogenic markers is defective and myoblast fusion into myotubes occurs without irreversible cell cycle exit. This evidence demonstrates only a partial functional redundancy between pRb and its relatives p107 and pRb2/p130, as these pRb−/− multinucleated cells, which display p107 levels higher than normal myotubes, respond to mitogens with cell cycle re-entry and DNA synthesis. At the molecular level, pRb myogenic functions are mediated by cooperation with MyoD, Myocyte enhancer factor 2 (MEF2), High mobility group box protein-1 (HBP1) and histone deacetylase1, affecting chromatin configuration and tissue-specific transcription, and by post-translational modification in response to intracellular signaling cascades.

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References

  • Aslanian A, Iaquinta PJ, Verona R, Lees JA . (2004). Genes Dev 18: 1413–1422.

  • Bagella L, MacLachlan TK, Buono RJ, Pisano MM, Giordano A, De Luca A . (1998). J Cell Physiol 177: 206–213.

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

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

  • De Luca A, MacLachlan TK, Bagella L, Dean C, Howard CM, Claudio PP et al. (1997). J Biol Chem 272: 20971–20974.

  • Dimova DK, Stevaux O, Frolov MV, Dyson NJ . (2003). Genes Dev 17: 2308–2320.

  • Dyson N . (1998). Genes Dev 12: 2245–2262.

  • Falls HF, Neel JV . (1951). AMA Arch Ophthalmol 46: 367–389.

  • Flemington EK, Speck SH, Kaelin Jr WG . (1993). Proc Natl Acad Sci USA 90: 6914–6918.

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

  • Frolov MV, Dyson NJ . (2004). J Cell Sci 117 (Part 11): 2173–2181.

  • Giacinti C, Bagella L, Puri PL, Giordano A, Simone C . (2006). J Cell Physiol 206: 807–813.

  • Ginsberg D . (2004). Dev Cell 6: 742–743.

  • Grana X, Luca A, Sang N, Fu Y, Claudio PP, Rosenblatt J et al. (1994). Proc Natl Acad Sci USA 91: 3834–3838.

  • Gu W, Schneider JW, Condorelli G, Kaushal S, Mahdavi V, Nadal-Ginard B . (1993). Cell 72: 309–324.

  • Guo K, Walsh K . (1997). J Biol Chem 272: 791–797.

  • Halevy O, Novitch BG, Spicer DB, Skapek SX, Rhee J, Hannon GJ et al. (1995). Science 267: 1018–1021.

  • Helin K, Ed H . (1993). Trends Cell Biol 3: 43–46.

  • Iezzi S, Di Padova M, Serra C, Caretti G, Simone C, Maklan E et al. (2004). Dev Cell 6: 673–684.

  • Kitzmann M, Vandromme M, Schaeffer V, Carnac G, Labbe JC, Lamb N et al. (1999). Mol Cell Biol 19: 3167–3176.

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

  • Lachner M, O'Sullivan RJ, Jenuwein T . (2003). J Cell Sci 116 (Part 11): 2117–2124.

  • Leone G, Nuckolls F, Ishida S, Adams M, Sears R, Jakoi L et al. (2000). Mol Cell Biol 20: 3626–3632.

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

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

  • Muller H, Bracken AP, Vernell R, Moroni MC, Christians F, Grassilli E et al. (2001). Genes Dev 15: 267–285.

  • Nevins JR . (1992). Science 258: 424–429.

  • Nguyen DX, Baglia LA, Huang SM, Baker CM, McCance DJ . (2004). EMBO J 23: 1609–1618 [E-pub ahead of print 2004 Mar 25. 15].

  • Novitch BG, Mulligan GJ, Jacks T, Lassar AB . (1996). J Cell Biol 135: 441–456.

  • Novitch BG, Spicer DB, Kim PS, Cheung WL, Lassar AB . (1999). Curr Biol 9: 449–459.

  • Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A et al. (1995). Science 267: 1024–1027.

  • Puri PL, Balsano C, Burgio VL, Chirillo P, Natoli G, Ricci L et al. (1997). Oncogene 14: 1171–1184.

  • Puri PL, Iezzi S, Stiegler P, Chen TT, Schiltz RL, Muscat GE et al. (2001). Mol Cell 8: 885–897.

  • Puri PL, Sartorelli V . (2000). J Cell Physiol 85: 155–173.

  • Sellers WR, Kaelin WG . (1996). Biochim Biophys Acta 1288: M1–M5 (Review. Erratum in: Biochim Biophys Acta 1996 Dec 9; 1288(3)).

  • Sellers WR, Novitch BG, Miy'ake S, Heith A, Otterson GA, Kaye FJ et al. (1998). Genes Dev 12: 95–106.

  • Shih HH, Tevosian SG, Yee AS . (1998). Mol Cell Biol 18: 4732–4743.

  • Simone C . (2005). J Cell Physiol 207: 309–314.

  • Simone C, Bagella L, Bellan C, Giordano A . (2002a). Oncogene 21: 4158–4165.

  • Simone C, Forcales SV, Hill DA, Imbalzano AN, Latella L, Puri PL . (2004b). Nat Genet 36: 738–743.

  • Simone C, Giordano A . (2001). Front Biosci 6: D1073–D1082 (review).

  • Simone C, Stiegler P, Bagella L, Pucci B, Bellan C, De Falco G et al. (2002b). Oncogene 21: 4137–4148.

  • Simone C, Stiegler P, Forcales SV, Bagella L, De Luca A, Sartorelli V et al. (2004a). Oncogene 23: 2177–2187.

  • Skapek SX, Rhee J, Kim PS, Novitch BG, Lassar AB . (1996). Mol Cell Biol 16: 7043–7053.

  • Smialowski P, Singh M, Mikolajka A, Majumdar S, Joy JK, Nalabothula N et al. (2005). Biochim Biophys Acta 1750: 48–60 [E-pub ahead of print 2005 Apr 14].

  • Song A, Wang Q, Goebl M, Harrington M . (1998). Mol Cell Biol 18: 4994–4999.

  • Tevosian SG, Shih HH, Mendelson KG, Sheppard KA, Paulson KE, Yee AS . (1997). Genes Dev 11: 383–396.

  • Walsh K, Perlman H . (1997). Curr Opin Genet Dev 7: 597–602 (review).

  • Weintraub H . (1993). Cell 75: 1241–1244 Review.

  • Zhang HS, Gavin M, Dahiya A, Postigo AA, Ma D, Luo RX et al. (2000). Cell 101: 79–89.

  • Zhang JM, Wei Q, Zhao X, Paterson BM . (1999a). EMBO J 18: 926–933.

  • Zhang JM, Zhao X, Wei Q, Paterson BM . (1999b). EMBO J 18: 6983–6993.

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Acknowledgements

We thank Marie Basso for her editorial assistance.

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Authors and Affiliations

  1. Department of Human Pathology and Oncology, University of Siena, Siena, Italy

    G De Falco

  2. Department of Biomedicine in Childhood, Division of Medical Genetics, University of Bari, Bari, Italy

    F Comes & C Simone

  3. Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA, USA

    G De Falco & C Simone

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Correspondence to C Simone.

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De Falco, G., Comes, F. & Simone, C. pRb: master of differentiation. Coupling irreversible cell cycle withdrawal with induction of muscle-specific transcription. Oncogene 25, 5244–5249 (2006). https://doi.org/10.1038/sj.onc.1209623

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