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  • Original Paper
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The polycomb protein MPc3 interacts with AF9, an MLL fusion partner in t(9;11)(p22;q23) acute leukemias

Oncogene volume 20, pages 3798–3805 (2001)Cite this article

Abstract

Polycomb group (PcG) proteins assemble to form large multiprotein complexes involved in gene silencing. Evidence suggests that PcG complexes are heterogeneous with respect to both protein composition and specific function. MPc3 is a recently described mouse Polycomb (Pc) protein that shares structural homology with at least two other Pc proteins, M33 and MPc2. All three Pc proteins bind another PcG protein, RING1, through a conserved carboxy-terminal C-box motif. Here, data are presented demonstrating that MPc3 also interacts with AF9, a transcriptional activator implicated in the development of acute leukemias. The carboxy-terminus of AF9 is fused to the MLL protein in leukemias characterized by t(9;11)(p22;q23) chromosomal translocations. Importantly, it is the carboxy-terminus of AF9 to which MPc3 binds. The AF9 binding site of MPc3 maps to a central, non-conserved, region of the polypeptide sequence. In contrast to MPc3, data indicate that the Pc protein M33 does not interact with AF9. This finding suggests a potentially unique role for MPc3 in linking a PcG silencing complex to a transcriptional activator protein.

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References

  • Alkema MJ, Jacobs J, Voncken JW, Jenkins NA, Copeland NG, Satijn DPE, Otte AP, Berns A, van Lohuizen M . 1997a J. Mol. Biol. 273: 993–1003

  • Alkema MJ, Bronk M, Verhoeven E, Otte A, van't Veer LJ, Berns A, van Lohuizen M . 1997b Genes Dev. 11: 226–240

  • Bárdos JL, Saurin AJ, Tissot C, Duprez E, Freemont PS . 2000 J. Biol. Chem. 275: 28785–28792

  • Bel S, Coré N, Djabali M, Klieboom K, van der Lugt N, Alkema MJ, van Lohuizen M . 1998 Development 125: 3543–3551

  • Bunker CA, Kingston RE . 1994 Mol. Cell. Biol. 14: 1721–1732

  • Corral J, Lavenir I, Impey H, Warren AJ, Forster A, Larson TA, Bell S, McKenzie ANJ, King G, Rabbits TH . 1996 Cell 85: 853–861

  • Franke A, DeCamillis M, Zink D, Chang N, Brock HW, Paro R . 1992 EMBO J. 11: 2941–2950

  • Garcia-Cuéllar MP, Zilles O, Schreiner SA, Birke M, Winkler TH, Slang RK . 2001 Oncogene 20: 411–419

  • Gunster MJ, Satijn DPE, Hamer KM, den Blaauwen JL, de Bruijn D, Alkema MJ, van Lohuizen M, van Driel R, Otte AP . 1997 Mol. Cell. Biol. 17: 2326–2335

  • Hashimoto N, Brock HW, Nomura M, Kyba M, Hodgson J, Fujita Y, Takihara Y, Shimada K, Higashinakagawa T . 1998 Biochem. Biophys. Res. Comm. 245: 356–365

  • Hemenway CS, Halligan BW, Levy LS . 1998 Oncogene 16: 2541–2547

  • Hemenway CS, Halligan BW, Gould GCD, Levy LS . 2000 Gene 242: 31–40

  • Horard B, Tatout C, Poux S, Pirrotta V . 2000 Mol. Cell. Biol. 20: 3187–3197

  • Iida S, Seto M, Yamamoto K, Komatsu H, Tojo A, Asano S, Kamada N, Ariyoshi Y . 1993 Oncogene. 8: 3085–3092

  • Jürgens G . 1985 Nature 316: 153–155

  • Morgan H, Smith M, Burke Z, Carter D . 2000 FASEB J. 14: 1109–1116

  • Nakamura T, Alder H, Gu Y, Prasad R, Canaani O, Kamada N, Gale RP, Lange B, Crist WM, Nowell PC, Croce CM, Canaani E . 1993 Proc. Natl. Acad. Sci. USA 90: 4631–4635

  • Pearce JJH, Singh PB, Gaunt SJ . 1992 Development 114: 921–929

  • Peterson AJ, Kyba M, Bornemann D, Morgan K, Brock HW, Simon J . 1997 Mol. Cell. Biol. 17: 6683–6692

  • Pirrotta V . 1997 Trends Genet. 13: 314–318

  • Pirrotta V . 1998 Cell 93: 333–336

  • Rubnitz JE, Morrissey J, Savage PA, Cleary ML . 1994 Blood 84: 1747–1752

  • Satijn DPE, Gunster MJ, van der Vlag J, Hamer KM, Schul W, Alkema MJ, Saurin AJ, Freemont PS, van Driel R, Otte AP . 1997 Mol. Cell. Biol. 17: 4105–4113

  • Satijn DPE, Otte AP . 1999 Mol. Cell. Biol. 19: 57–68

  • Schoorlemmer J, Marcos-Gutierrez C, Were F, Martinez R, Garcia E, Satijn DPE, Otte AP, Vidal M . 1997 EMBO J. 16: 5930–5942

  • Schumacher A, Magnuson T . 1997 Trends Genet. 13: 167–170

  • Sewalt RGAB, van der Vlag J, Gunster MJ, Hamer KM, den Blaauwen JL, Satijn DPE, Hendrix T, van Driel R, Otte AP . 1998 Mol. Cell. Biol. 18: 3586–3595

  • Sewalt RGAB, Gunster MJ, van der Vlag J, Satijn DPE, Otte AP . 1999 Mol. Cell. Biol. 19: 777–787

  • Shao Z, Raible F, Mollaaghababa R, Guyon J, Wu C, Bender W, Kingston RE . 1999 Cell 98: 37–46

  • Slany RK, Lavau C, Cleary ML . 1998 Mol. Cell. Biol. 18: 122–129

  • Strutt H, Cavalli G, Paro R . 1997 EMBO J. 16: 3621–3632

  • Strutt H, Paro A . 1997 Mol. Cell. Biol. 17: 6773–6783

  • Takihara Y, Tomotsune D, Shirai M, Katoh-Fukui Y, Nishii K, Motalab MA, Nomura M, Tsuchiya R, Fujita Y, Shibata Y, Higashinakagawa T, Shimada K . 1997 Development 124: 3673–3682

  • van der Lugt NMT, Domen J, Linders K, van Roon M, Robanus-Maandag E, te Riele H, van der Valk M, Deschamps J, Sofroniew M, van Lohuizen M, Berns M . 1994 Genes Dev. 8: 757–769

  • van der Vlag J, Otte A . 1999 Nat. Genet. 23: 474–478

  • van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens T . 1998 Mol. Cell. Biol. 18: 3572–3579

  • van Lohuizen M . 1999 Curr. Opin. Cell. Biol. 9: 355–361

  • Yamamoto Y, Girard F, Bello B, Affolter M, Gehrig WJ . 1997 Development 124: 3385–3394

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Acknowledgements

We thank Masao Seto, Malek Djabali, Erik Flemington and Charles Miller for plasmids and reagents. Laura Levy and Charles Scher have been instrumental in the development of this project. This work was supported in part by the Louisiana Board of Regents Support Fund [LEQSF (1998-01)-RD-A-32] and the National Institutes of Health (1 K01 CA78318-01A1).

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Authors and Affiliations

  1. Department of Pediatrics, Tulane University School of Medicine, New Orleans, 70112, Louisiana, LA, USA

    Charles S Hemenway, Andrea C de Erkenez & Grahame C D Gould

  2. Tulane Cancer Center, Tulane University School of Medicine, New Orleans, 70112, Louisiana, LA, USA

    Charles S Hemenway, Andrea C de Erkenez & Grahame C D Gould

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  1. Charles S Hemenway
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  2. Andrea C de Erkenez
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Correspondence to Charles S Hemenway.

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Hemenway, C., de Erkenez, A. & Gould, G. The polycomb protein MPc3 interacts with AF9, an MLL fusion partner in t(9;11)(p22;q23) acute leukemias. Oncogene 20, 3798–3805 (2001). https://doi.org/10.1038/sj.onc.1204478

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