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  • Original Paper
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The promyelocytic leukemia (PML) protein suppresses cyclin D1 protein production by altering the nuclear cytoplasmic distribution of cyclin D1 mRNA

Oncogene volume 19, pages 1623–1634 (2000)Cite this article

Abstract

The majority of the promyelocytic leukemia (PML) protein is present in nuclear bodies which are altered in several pathogenic conditions including acute promyelocytic leukemia. PML nuclear bodies are found in nearly all cells yet their function remains unknown. Here, we demonstrate that PML and the eukaryotic initiation factor 4E (eIF-4E) co-localize and co-immunopurify. eIF-4E is involved in nucleocytoplasmic transport of specific mRNAs including cyclin D1. eIF-4E overexpression leads to increased cyclin D1 protein levels; whereas, overexpression of PML leads to decreased cyclin D1 levels. Neither PML nor eIF-4E cause significant changes in cyclin D1 mRNA levels. The association with eIF-4E led us to investigate if PML could alter mRNA distribution as a possible post-transcriptional mechanism for suppressing cyclin D1 production. We show that overexpression of PML results in nuclear retention of cyclin D1 mRNA and that intact PML nuclear bodies are required. Addition of eIF-4E overcomes PML induced retention and alters the morphology of PML bodies suggesting a mechanism by which eIF-4E can modulate PML function. These results raise the possibility that PML nuclear bodies may participate in the regulation of nucleocytoplasmic transport of specific mRNAs.

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References

  • Alcalay M, Tomassoni L, Colombo E, Stoldt S, Grignan F, Fagioli M, Skekely L, Helin K and Pelicci PG . 1998 Mol Cell Biol 18: 1084–1093

  • Boddy MN, Howe K, Etkin LD, Solomon E and Freemont PS . 1996 Oncogene 13: 971–982

  • Boddy MN, Duprez E, Borden KLB and Freemont PS . 1997 J Cell Sci 110: 2197–2205

  • Borden KLB, Campbell Dwyer EJ and Salvato MS . 1998a J Virol 72: 758–766

  • Borden KLB, Campbell Dwyer EJ, Carlile GW, Djavani M and Salvato MS . 1998b J Virol 72: 3819–3826

  • Borden KLB, Campbell Dwyer EJ and Salvato MS . 1997 FEBS Lett 418: 30–34

  • Borden KLB, Boddy MN, Lally J, O'Reilly NJ, Martin S, Howe K, Solomon E and Freemont PS . 1995 EMBO J 14: 1532–1541

  • Borden KLB, Lally JM, Martin SR, O'Reilly NJ, Solomon E and Freemont PS . 1996 Proc Natl Acad Sci USA 93: 1601–1606

  • Campbell Dwyer EJ, Lai HK, MacDonald RC, Salvato MS and Borden KLB . 2000 J Virol in press

  • Carlile GW, Tatton WG and Borden KLB . 1998 Biochemical J 335: 691–696

  • Fagioli M, Alcalay M, Pandolfi PP, Venturini L, Mencarelli A, Simeone A, Acampora D, Grignani F and Pelici PG . 1992 Oncogene 7: 1083–1091

  • Ferrucci PF, Grignani F, Pearson M, Fagioli M, Nicoletti I and Pelici PG . 1997 Proc Natl Acad Sci USA 94: 10901–10906

  • Flenghi L, Fagioli M, Tomassoni L, Pileri S, Gambacorta M, Pacini R, Grignani F, Casini T, Ferrucci PF, Martelli MF, Pelici PG and Falini B . 1995 Blood 85: 1871–1880

  • Grande MA, van der Kraan I, van Steensel B, Schul W, de The H, van der Voort HT, de Jong L and van Driel R . 1996 J Cell Biochem 63: 280–291

  • Hunter T and Pines J . 1994 Cell 79: 573–582

  • Kentsis A and Borden KLB . 2000 Curr Opin Prot and Peptide Sci in press

  • Koken MHM, Puvion-Dutilleul F, Guillemin MC, Viron V, Linares-Cruz G, Stuurman N, de Jong L, Szostecki C, Calvo F, Chomienne C and de The H . 1994 EMBO J 13: 1073–1083

  • Knudsen KE, Cavenee WK and Arden KC . 1999 Cancer Res 59: 2297–2301

  • LaMorte VJ, Dyck JA, Ochs RL and Evans RM . 1998 Proc Natl Acad Sci 95: 4991–4996

  • Le XF, Yang P and Chang KS . 1996 J Biol Chem 271: 130–135

  • Le XF, Vallian S, Mu ZM, Hung MC and Chang KS . 1998 Oncogene 16: 1839–1849

  • Lejbkowicz F, Goyer C, Darveau A, Neron S, Lemieux R and Sonenberg N . 1992 Proc Natl Acad Sci 89: 9612–9616

  • Maul GG, Yu E, Ishov AM and Epstein AL . 1995 J Cell Biochem 59: 498–513

  • Mayfield S . 1996 Chem Biol 3: 415–418

  • McMahon C, Suthiphongchai T, DiRenzo J and Ewen ME . 1999 Proc Natl Acad Sci 96: 5382–5387

  • Melnick A and Licht JD . 1999 Blood 93: 3167–3215

  • Mu Z-M, Chin K-V, Liu J-H, Lozano G and Chang K-S . 1994 Mol Cell Biol 14: 6858–6867

  • Polunovsky VA, Rosenwald IB, Tan AT, White J, Chiang L, Sonenberg N and Bitterman PB . 1996 Mol Cell Biol 16: 6573–6581

  • Quignon F, DeBels F, Koken M, Feunteun J, Ameisen J-C and de The H . 1998 Nature Genetics 20: 259–265

  • Rosenwald IB, Kaspar R, Rousseau D, Gerkhe L, Leboulch P, Chen JJ, Schmidt EV, Sonenberg N and London IM . 1995 J Biol Chem 270: 21176–21180

  • Rousseau D, Kaspar R, Rosenwal I, Gehrke L and Sonenberg N . 1996 Proc Natl Acad Sci 93: 1065–1070

  • Saurin AJ, Borden KLB, Boddy MN and Freemont PS . 1996 Trends in Biochem Sci 246: 208–213

  • Singh R and Green MR . 1993 Science 259: 365–368

  • Stuurman N, De Graaf A, Floore A, Josso A, Humbel B, De Jong L and Van Driel R . 1992 J Cell Sci 101: 773–784

  • Stuurman N, Floore A, Middelkoop E, van Driel R and de Jong L . 1997 Cell Mol Biol Lett 2: 137–150

  • Terris B, Baldin V, Dubois S, Degott C, Flejou J-F, Henin D and Dejean A . 1995 Can Res 55: 1590–1597

  • Wang Z-G, Delva L, Gaboli M, Rivi R, Giorgi M, Cordon-Cardo C, Grosveld F and Pandolfi PP . 1998a Science 279: 1547–1551

  • Wang Z-G, Ruggero D, Ronchetti S, Zhong A, Gaboli M, Rivi R and Pandolfi PP . 1998b Nature Genetics 20: 266–272

  • Weis K, Rambaud S, Lavau C, Jansen J, Carvalho T, Carmo-Foneseca M, Lamond A and Dejean A . 1994 Cell 76: 345–356

  • Yacoub A, Kelley MR and Deutsch WA . 1996 Nuc Acids Res 24: 4298–4303

  • Ziemiecki A, Muller RG, Xiao-Chang F, Hynes NE and Kozma S . 1990 EMBO J 9: 191–196

  • Zwijsen RM, Buckle RS, Hijmans EM, Loomans CJ and Bernards R . 1998 Genes Devt 12: 3488–3498

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Acknowledgements

We are grateful for the kind gifts of the mAb 5E10 from L de Jong, and the polyclonal PML antibody from E Solomon and P Freemont. We thank N Gray, G Carlile, L Etkin, J Licht, M Salvato, A Melnick and especially S Pinol-Roma for critical discussions. KLB Borden acknowledges financial support from the NIH RO1 CA80728.

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  1. Department of Physiology & Biophysics, Mount Sinai School of Medicine, New York, 10029, NY, USA

    H-K Lai & K L B Borden

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Lai, HK., Borden, K. The promyelocytic leukemia (PML) protein suppresses cyclin D1 protein production by altering the nuclear cytoplasmic distribution of cyclin D1 mRNA. Oncogene 19, 1623–1634 (2000). https://doi.org/10.1038/sj.onc.1203473

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