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Regulation of cell lineage specification by the retinoblastoma tumor suppressor

Abstract

Early studies of the retinoblastoma gene (RB) have uncovered its critical role as a regulator of the G1/S cell cycle phase progression. Surprisingly, genetic approaches in mammals and nematodes have also shown RB controls cell lineage specification and aspects of differentiation. The RB gene product accomplishes this by diverse mechanisms such as by interacting with tissue-specific transcription factors, enhancing RNA interference, and modifying chromatin structure. We review recent studies uncovering novel mechanisms by which RB works in several cell lineages and we provide perspectives on how these new findings might relate to RB tumor suppression.

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References

  • Anderson KL, Smith KA, Conners K, McKercher SR, Maki RA, Torbett BE . (1998). Blood 91: 3702–3710.

  • Ashe M, Pabon-Pena L, Dees E, Price KL, Bader D . (2004). J Biol Chem 279: 664–676.

  • Benevolenskaya EV, Murray HL, Branton P, Young RA, Kaelin Jr WG . (2005). Mol Cell 18: 623–635.

  • Camarda G, Siepi F, Pajalunga D, Bernardini C, Rossi R, Montecucco A et al. (2004). J Cell Biol 167: 417–423.

  • Cardoso C, Couillault C, Mignon-Ravix C, Millet A, Ewbank JJ, Fontes M et al. (2005). Dev Biol 278: 49–59.

  • Cavenee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL et al. (1983). Nature (London) 305: 779–784.

  • Cederberg A, Gronning LM, Ahren B, Tasken K, Carlsson P, Enerback S . (2001). Cell 106: 563–573.

  • Ceol CJ, Horvitz HR . (2001). Mol Cell 7: 461–473.

  • Chen D, Livne-bar I, Vanderluit JL, Slack RS, Agochiya M, Bremner R . (2004). Cancer Cell 5: 539–551.

  • Chen G, Guy CT, Chen HW, Hu N, Lee EY, Lee WH . (1996a). J Biol Chem 271: 9567–9572.

  • Chen P-L, Riley DJ, Chen Y, Lee W-H . (1996b). Genes Dev 10: 2794–2804.

  • Clarke AR, Maandag ER, van Roon M, van der Lugt NMT, van der Valk M, Hooper ML et al. (1992). Nature 359: 328–330.

  • Classon M, Harlow E . (2002). Nat Rev Cancer 2: 910–917.

  • Cloud JE, Rogers C, Reza TL, Ziebold U, Stone JR, Picard MH et al. (2002). Mol Cell Biol 22: 2663–2672.

  • Collins J, Saari B, Anderson P . (1987). Nature 328: 726–728 8-26-1987.

  • Couteau F, Guerry F, Muller F, Palladino F . (2002). EMBO R 3: 235–241.

  • de Bruin A, Wu L, Saavedra HI, Wilson P, Yang Y, Rosol TJ et al. (2003). Proc Natl Acad Sci USA 100: 6546–6551.

  • DeKoter RP, Walsh JC, Singh H . (1998). EMBO J 17: 4456–4468.

  • Dimova DK, Dyson NJ . (2005). Oncogene 24: 2810–2826.

  • Ducy P, Schinke T, Karsenty G . (2000). Science 289: 1501–1504.

  • Ebel C, Mariconti L, Gruissem W . (2004). Nature 429: 776–780.

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

  • Fay DS, Large E, Han M, Darland M . (2003). Development 130: 3319–3330.

  • Ferguson EL, Horvitz HR . (1989). Genetics 123: 109–121.

  • Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC . (1998). Nature 391: 806–811.

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

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

  • Fung YKT, Murphree AL, T'Ang A, Qian J, Hinrichs SH, Benedict WF . (1987). Science 236: 1657–1661.

  • Godbout R, Dryja TP, Squire J, Gallie BL, Phillips RA . (1983). Nature 304: 451–453.

  • Grishok A, Tabara H, Mello CC . (2000). Science 287: 2494–2497.

  • Grishok A, Sinskey JL, Sharp PA . (2005). Genes Dev 19: 683–696.

  • Grishok A, Sharp PA . (2005). Proc Natl Acad Sci USA 102: 17360–17365.

  • Hall IM, Shankaranarayana GD, Noma KI, Ayoub N, Cohen A, Grewal SIS . (2002). Science 297: 2232–2237.

  • Hansen JB, Jorgensen C, Petersen RK, Hallenborg P, De MR, Boye HA et al. (2004). Proc Natl Acad Sci USA 101: 4112–4117.

  • Hernando E, Nahle Z, Juan G, az-Rodriguez E, Alaminos M, Hemann M et al. (2004). Nature 430: 797–802.

  • Hu N, Gulley ML, Kung JT, Lee EYHP . (1997). Cancer Res 57: 4123–4129.

  • Hu N, Gutsmann A, Herbert DC, Bradley A, Lee W-H, Lee EYHP . (1994). Oncogene 9: 1021–1027.

  • Huh MS, Parker MH, Scime A, Parks R, Rudnicki MA . (2004). J Cell Biol 166: 865–876.

  • Iavarone A, Garg P, Lasorella A, Hsu J, Israel MA . (1994). Genes Dev 8: 1270–1284.

  • Iavarone A, King ER, Dai XM, Leone G, Stanley ER, Lasorella A . (2004). Nature 432: 1040–1045.

  • Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA . (1992). Nature 359: 295–300.

  • Jackson MW, Agarwal MK, Yang J, Bruss P, Uchiumi T, Agarwal ML et al. (2005). J Cell Sci 118: 1821–1832.

  • Jenuwein T, Allis CD . (2001). Science 293: 1074–1080.

  • Kawane K, Fukuyama H, Kondoh G, Takeda J, Ohsawa Y, Uchiyama Y et al. (2001). Science 292: 1546–1549.

  • Kelly WG, Schaner CE, Dernburg AF, Lee MH, Kim SK, Villeneuve AM et al. (2002). Development 129: 479–492.

  • Ketting RF, Haverkamp THA, van Luenen HGAM, Plasterk RHA . (1999). Cell 99: 133–141.

  • Lasorella A, Noseda M, Beyna M, Yokota Y, Iavarone A . (2000). Nature 407: 592–598.

  • Lee EY, Chang CY, Hu N, Wang YC, Lai CC, Herrup K et al. (1992). Nature 359: 288–294.

  • Lee KY, Ladha MH, McMahon C, Ewen ME . (1999). Mol Cell Biol 19: 7724–7732.

  • Lee W-H, Bookstein R, Hong F, Young L-J, Shew J-Y, Lee EYHP . (1987). Science 235: 1394–1399.

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

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

  • Maandag ECR, van der Valk M, Vlaar M, Feltkamp C, O'Brien J, van Roon M et al. (1994). EMBO J 13: 4260–4268.

  • MacPherson D, Sage J, Kim T, Ho D, McLaughlin ME, Jacks T . (2004). Genes Dev 18: 1681–1694.

  • Maison C, Almouzni G . (2004). Nat Rev Mol Cell Biol 5: 296–304.

  • Mansouri A, Chowdhury K, Gruss P . (1998). Nat Genet 19: 83–86.

  • Mantela J, Jiang Z, Ylikoski J, Fritzsch B, Zacksenhaus E, Pirvola U . (2005). Development 132: 2377–2388.

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

  • Meuwissen R, Linn SC, Linnoila RI, Zevenhoven J, Mooi WJ, Berns A . (2003). Cancer Cell 4: 181–189.

  • Miccadei S, Provenzano C, Mojzisek M, Natali PG, Civitareale D . (2005). Oncogene 24: 6993–7001.

  • Minna JD, Roth JA, Gazdar AF . (2002). Cancer Cell 1: 49–52.

  • Myers TR, Greenwald I . (2005). Dev Cell 8: 117–123.

  • Nikitin AY, Juarez-Perez MI, Li S, Huang L, Lee WH . (1999). Proc Natl Acad Sci USA 96: 3916–3921.

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

  • Papadimou E, Menard C, Grey C, Puceat M . (2005). EMBO J 24: 1750–1761.

  • Picard F, Gehin M, Annicotte J, Rocchi S, Champy MF, O'Malley BW et al. (2002). Cell 111: 931–941.

  • Puigserver P, Ribot J, Serra F, Gianotti M, Bonet ML, Nadal-Ginard B et al. (1998a). Eur J Cell Biol 77: 117–123.

  • Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM . (1998b). Cell 92: 829–839.

  • Qian YW, Wang YC, Hollingsworth Jr RE, Jones D, Ling N, Lee EY . (1993). Nature 364: 648–652.

  • Qiu X, Fay DS . (2006). Dev Biol 291: 239–252.

  • Rekhtman N, Choe KS, Matushansky I, Murray S, Stopka T, Skoultchi AI . (2003). Mol Cell Biol 23: 7460–7474.

  • Robanus-Maandag E, Dekker M, van der Valk M, Carrozza M-L, Jeanny J-C, Dannenberg J-H et al. (1998). Genes Dev 12: 1599–1609.

  • Sage C, Huang M, Karimi K, Gutierrez G, Vollrath MA, Zhang D-S et al. (2005). Science 307: 1114–1118.

  • Schneider JW, Gu W, Zhu L, Mahdavi V, Nadal-Ginard B . (1994). Science 264: 1467–1471.

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

  • Sijen T, Plasterk RHA . (2003). Nature 426: 310–314.

  • Skapek SX, Lin S-CJ, Jablonski MM, McKeller RN, Tan M, Hu N et al. (2001). Oncogene 20: 6742–6751.

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

  • Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al. (2004). Nature 432: 396–401.

  • Srivastava D, Olson EN . (2000). Nature 407: 221–226.

  • Takahashi C, Bronson RT, Socolovsky M, Contreras B, Lee KY, Jacks T et al. (2003). Mol Cell Biol 23: 5256–5268.

  • Takahashi C, Contreras B, Bronson RT, Loda M, Ewen ME . (2004). Mol Cell Biol 24: 10406–10415.

  • Thomas DM, Carty SA, Piscopo DM, Lee JS, Wang WF, Forrester WC et al. (2001). Mol Cell 8: 303–316.

  • Tsai KY, Hu Y, Macleod KF, Crowley D, Yamasaki L, Jacks T . (1998). Mol Cell 2: 293–304.

  • Volpe TA, Kidner C, Hall IM, Teng G, Grewal SIS, Martienssen RA . (2002). Science 297: 1833–1837.

  • Wang D, Kennedy S, Conte Jr D, Kim JK, Gabel HW, Kamath RS et al. (2005). Nature 436: 593–597.

  • Wikenheiser-Brokamp KA . (2006). Cell Mol Life Sci [E-pub ahead of print].

  • Wikenheiser-Brokamp KA . (2004). Development 131: 4299–4310.

  • Wildwater M, Campilho A, Perez-Perez JM, Heidstra R, Blilou I, Korthout H et al. (2005). Cell 123: 1337–1349.

  • Williams BO, Schmitt EM, Remington L, Bronson RT, Albert DM, Weinberg RA et al. (1994). EMBO J 13: 4251–4259.

  • Wu L, de BA, Saavedra HI, Starovic M, Trimboli A, Yang Y et al. (2003). Nature 421: 942–947.

  • Wylie C . (1999). Cell 96: 165–174.

  • Yuan SS, Yeh YT, Lee E . (2002). Biochem Biophys Res Commun 296: 1019–1025.

  • Zacksenhaus E, Jiang Z, Chung D, Marth JD, Phillips RA, Gallie BL . (1996). Genes Dev 10: 3051–3064.

  • Zhang J, Gray J, Wu L, Leone G, Rowan S, Cepko CL et al. (2004a). Nat Genet 36: 351–360.

  • Zhang J, Schweers B, Dyer MA . (2004b). Cell Cycle 3: 952–959.

  • Zhang P, Wong C, DePinho RA, Harper JW, Elledge SJ . (1998). Genes Dev 12: 3162–3167.

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

  • Ziebold U, Reza T, Caron A, Lees JA . (2001). Genes Dev 15: 386–391.

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Correspondence to S X Skapek or E Y-H P Lee.

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Skapek, S., Pan, YR. & Lee, EH. Regulation of cell lineage specification by the retinoblastoma tumor suppressor. Oncogene 25, 5268–5276 (2006). https://doi.org/10.1038/sj.onc.1209710

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