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. 1998 Aug;63(2):297–304. doi: 10.1086/301991

Structure, organization, and dynamics of promyelocytic leukemia protein nuclear bodies.

M Hodges 1, C Tissot 1, K Howe 1, D Grimwade 1, P S Freemont 1
PMCID: PMC1377331  PMID: 9683622

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Selected References

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  1. Ahn M. J., Langenfeld J., Moasser M. M., Rusch V., Dmitrovsky E. Growth suppression of transformed human bronchial epithelial cells by all-trans-retinoic acid occurs through specific retinoid receptors. Oncogene. 1995 Dec 7;11(11):2357–2364. [PubMed] [Google Scholar]
  2. Alcalay M., Tomassoni L., Colombo E., Stoldt S., Grignani F., Fagioli M., Szekely L., Helin K., Pelicci P. G. The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein. Mol Cell Biol. 1998 Feb;18(2):1084–1093. doi: 10.1128/mcb.18.2.1084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ascoli C. A., Maul G. G. Identification of a novel nuclear domain. J Cell Biol. 1991 Mar;112(5):785–795. doi: 10.1083/jcb.112.5.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boddy M. N., Duprez E., Borden K. L., Freemont P. S. Surface residue mutations of the PML RING finger domain alter the formation of nuclear matrix-associated PML bodies. J Cell Sci. 1997 Sep;110(Pt 18):2197–2205. doi: 10.1242/jcs.110.18.2197. [DOI] [PubMed] [Google Scholar]
  5. Boddy M. N., Howe K., Etkin L. D., Solomon E., Freemont P. S. PIC 1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia. Oncogene. 1996 Sep 5;13(5):971–982. [PubMed] [Google Scholar]
  6. Borden K. L., Boddy M. N., Lally J., O'Reilly N. J., Martin S., Howe K., Solomon E., Freemont P. S. The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J. 1995 Apr 3;14(7):1532–1541. doi: 10.1002/j.1460-2075.1995.tb07139.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Borden K. L., Campbell Dwyer E. J., Salvato M. S. An arenavirus RING (zinc-binding) protein binds the oncoprotein promyelocyte leukemia protein (PML) and relocates PML nuclear bodies to the cytoplasm. J Virol. 1998 Jan;72(1):758–766. doi: 10.1128/jvi.72.1.758-766.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Borden K. L., Lally J. M., Martin S. R., O'Reilly N. J., Solomon E., Freemont P. S. In vivo and in vitro characterization of the B1 and B2 zinc-binding domains from the acute promyelocytic leukemia protooncoprotein PML. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1601–1606. doi: 10.1073/pnas.93.4.1601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brown D., Kogan S., Lagasse E., Weissman I., Alcalay M., Pelicci P. G., Atwater S., Bishop J. M. A PMLRARalpha transgene initiates murine acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2551–2556. doi: 10.1073/pnas.94.6.2551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cao T., Duprez E., Borden K. L., Freemont P. S., Etkin L. D. Ret finger protein is a normal component of PML nuclear bodies and interacts directly with PML. J Cell Sci. 1998 May;111(Pt 10):1319–1329. doi: 10.1242/jcs.111.10.1319. [DOI] [PubMed] [Google Scholar]
  11. Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J. 1996 Jul;10(9):940–954. [PubMed] [Google Scholar]
  12. Chelbi-Alix M. K., Quignon F., Pelicano L., Koken M. H., de Thé H. Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein. J Virol. 1998 Feb;72(2):1043–1051. doi: 10.1128/jvi.72.2.1043-1051.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Darnell J. E., Jr, Kerr I. M., Stark G. R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. doi: 10.1126/science.8197455. [DOI] [PubMed] [Google Scholar]
  14. Desbois C., Rousset R., Bantignies F., Jalinot P. Exclusion of Int-6 from PML nuclear bodies by binding to the HTLV-I Tax oncoprotein. Science. 1996 Aug 16;273(5277):951–953. doi: 10.1126/science.273.5277.951. [DOI] [PubMed] [Google Scholar]
  15. Doucas V., Evans R. M. The PML nuclear compartment and cancer. Biochim Biophys Acta. 1996 Dec 9;1288(3):M25–M29. doi: 10.1016/s0304-419x(96)00028-5. [DOI] [PubMed] [Google Scholar]
  16. Doucas V., Ishov A. M., Romo A., Juguilon H., Weitzman M. D., Evans R. M., Maul G. G. Adenovirus replication is coupled with the dynamic properties of the PML nuclear structure. Genes Dev. 1996 Jan 15;10(2):196–207. doi: 10.1101/gad.10.2.196. [DOI] [PubMed] [Google Scholar]
  17. Dyck J. A., Maul G. G., Miller W. H., Jr, Chen J. D., Kakizuka A., Evans R. M. A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell. 1994 Jan 28;76(2):333–343. doi: 10.1016/0092-8674(94)90340-9. [DOI] [PubMed] [Google Scholar]
  18. Everett R. D., Freemont P., Saitoh H., Dasso M., Orr A., Kathoria M., Parkinson J. The disruption of ND10 during herpes simplex virus infection correlates with the Vmw110- and proteasome-dependent loss of several PML isoforms. J Virol. 1998 Aug;72(8):6581–6591. doi: 10.1128/jvi.72.8.6581-6591.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Everett R. D., Maul G. G. HSV-1 IE protein Vmw110 causes redistribution of PML. EMBO J. 1994 Nov 1;13(21):5062–5069. doi: 10.1002/j.1460-2075.1994.tb06835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Everett R. D., Meredith M., Orr A., Cross A., Kathoria M., Parkinson J. A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO J. 1997 Apr 1;16(7):1519–1530. doi: 10.1093/emboj/16.7.1519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fagioli M., Alcalay M., Tomassoni L., Ferrucci P. F., Mencarelli A., Riganelli D., Grignani F., Pozzan T., Nicoletti I., Grignani F. Cooperation between the RING + B1-B2 and coiled-coil domains of PML is necessary for its effects on cell survival. Oncogene. 1998 Jun 4;16(22):2905–2913. doi: 10.1038/sj.onc.1201811. [DOI] [PubMed] [Google Scholar]
  22. Ferreira J., Paolella G., Ramos C., Lamond A. I. Spatial organization of large-scale chromatin domains in the nucleus: a magnified view of single chromosome territories. J Cell Biol. 1997 Dec 29;139(7):1597–1610. doi: 10.1083/jcb.139.7.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gongora C., David G., Pintard L., Tissot C., Hua T. D., Dejean A., Mechti N. Molecular cloning of a new interferon-induced PML nuclear body-associated protein. J Biol Chem. 1997 Aug 1;272(31):19457–19463. doi: 10.1074/jbc.272.31.19457. [DOI] [PubMed] [Google Scholar]
  24. Grande M. A., van der Kraan I., van Steensel B., Schul W., de Thé H., van der Voort H. T., de Jong L., van Driel R. PML-containing nuclear bodies: their spatial distribution in relation to other nuclear components. J Cell Biochem. 1996 Dec 1;63(3):280–291. doi: 10.1002/(sici)1097-4644(19961201)63:3<280::aid-jcb3>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  25. Grignani F., De Matteis S., Nervi C., Tomassoni L., Gelmetti V., Cioce M., Fanelli M., Ruthardt M., Ferrara F. F., Zamir I. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature. 1998 Feb 19;391(6669):815–818. doi: 10.1038/35901. [DOI] [PubMed] [Google Scholar]
  26. Grignani F., Testa U., Rogaia D., Ferrucci P. F., Samoggia P., Pinto A., Aldinucci D., Gelmetti V., Fagioli M., Alcalay M. Effects on differentiation by the promyelocytic leukemia PML/RARalpha protein depend on the fusion of the PML protein dimerization and RARalpha DNA binding domains. EMBO J. 1996 Sep 16;15(18):4949–4958. [PMC free article] [PubMed] [Google Scholar]
  27. Grimwade D., Gorman P., Duprez E., Howe K., Langabeer S., Oliver F., Walker H., Culligan D., Waters J., Pomfret M. Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia. Blood. 1997 Dec 15;90(12):4876–4885. [PubMed] [Google Scholar]
  28. Grimwade D., Solomon E. Characterisation of the PML/RAR alpha rearrangement associated with t(15;17) acute promyelocytic leukaemia. Curr Top Microbiol Immunol. 1997;220:81–112. doi: 10.1007/978-3-642-60479-9_6. [DOI] [PubMed] [Google Scholar]
  29. Grisolano J. L., Wesselschmidt R. L., Pelicci P. G., Ley T. J. Altered myeloid development and acute leukemia in transgenic mice expressing PML-RAR alpha under control of cathepsin G regulatory sequences. Blood. 1997 Jan 15;89(2):376–387. [PubMed] [Google Scholar]
  30. Guidez F., Ivins S., Zhu J., Söderström M., Waxman S., Zelent A. Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia. Blood. 1998 Apr 15;91(8):2634–2642. [PubMed] [Google Scholar]
  31. He L. Z., Guidez F., Tribioli C., Peruzzi D., Ruthardt M., Zelent A., Pandolfi P. P. Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL. Nat Genet. 1998 Feb;18(2):126–135. doi: 10.1038/ng0298-126. [DOI] [PubMed] [Google Scholar]
  32. He L. Z., Tribioli C., Rivi R., Peruzzi D., Pelicci P. G., Soares V., Cattoretti G., Pandolfi P. P. Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5302–5307. doi: 10.1073/pnas.94.10.5302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ishov A. M., Maul G. G. The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition. J Cell Biol. 1996 Aug;134(4):815–826. doi: 10.1083/jcb.134.4.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ishov A. M., Stenberg R. M., Maul G. G. Human cytomegalovirus immediate early interaction with host nuclear structures: definition of an immediate transcript environment. J Cell Biol. 1997 Jul 14;138(1):5–16. doi: 10.1083/jcb.138.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jackson D. A. Nuclear organization: uniting replication foci, chromatin domains and chromosome structure. Bioessays. 1995 Jul;17(7):587–591. doi: 10.1002/bies.950170704. [DOI] [PubMed] [Google Scholar]
  36. Kamei H. Cystine starvation induces reversible large-body formation from nuclear bodies in T24 cells. Exp Cell Res. 1997 Nov 25;237(1):207–216. doi: 10.1006/excr.1997.3790. [DOI] [PubMed] [Google Scholar]
  37. Kastner P., Perez A., Lutz Y., Rochette-Egly C., Gaub M. P., Durand B., Lanotte M., Berger R., Chambon P. Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins. EMBO J. 1992 Feb;11(2):629–642. doi: 10.1002/j.1460-2075.1992.tb05095.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kelly C., Van Driel R., Wilkinson G. W. Disruption of PML-associated nuclear bodies during human cytomegalovirus infection. J Gen Virol. 1995 Nov;76(Pt 11):2887–2893. doi: 10.1099/0022-1317-76-11-2887. [DOI] [PubMed] [Google Scholar]
  39. Koken M. H., Linares-Cruz G., Quignon F., Viron A., Chelbi-Alix M. K., Sobczak-Thépot J., Juhlin L., Degos L., Calvo F., de Thé H. The PML growth-suppressor has an altered expression in human oncogenesis. Oncogene. 1995 Apr 6;10(7):1315–1324. [PubMed] [Google Scholar]
  40. Koken M. H., Reid A., Quignon F., Chelbi-Alix M. K., Davies J. M., Kabarowski J. H., Zhu J., Dong S., Chen S., Chen Z. Leukemia-associated retinoic acid receptor alpha fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10255–10260. doi: 10.1073/pnas.94.19.10255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Korioth F., Maul G. G., Plachter B., Stamminger T., Frey J. The nuclear domain 10 (ND10) is disrupted by the human cytomegalovirus gene product IE1. Exp Cell Res. 1996 Nov 25;229(1):155–158. doi: 10.1006/excr.1996.0353. [DOI] [PubMed] [Google Scholar]
  42. LaMorte V. J., Dyck J. A., Ochs R. L., Evans R. M. Localization of nascent RNA and CREB binding protein with the PML-containing nuclear body. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4991–4996. doi: 10.1073/pnas.95.9.4991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lamond A. I., Earnshaw W. C. Structure and function in the nucleus. Science. 1998 Apr 24;280(5363):547–553. doi: 10.1126/science.280.5363.547. [DOI] [PubMed] [Google Scholar]
  44. Le X. F., Vallian S., Mu Z. M., Hung M. C., Chang K. S. Recombinant PML adenovirus suppresses growth and tumorigenicity of human breast cancer cells by inducing G1 cell cycle arrest and apoptosis. Oncogene. 1998 Apr 9;16(14):1839–1849. doi: 10.1038/sj.onc.1201705. [DOI] [PubMed] [Google Scholar]
  45. Le X. F., Yang P., Chang K. S. Analysis of the growth and transformation suppressor domains of promyelocytic leukemia gene, PML. J Biol Chem. 1996 Jan 5;271(1):130–135. doi: 10.1074/jbc.271.1.130. [DOI] [PubMed] [Google Scholar]
  46. Lin R. J., Nagy L., Inoue S., Shao W., Miller W. H., Jr, Evans R. M. Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature. 1998 Feb 19;391(6669):811–814. doi: 10.1038/35895. [DOI] [PubMed] [Google Scholar]
  47. Matera A. G., Frey M. R. Coiled bodies and gems: Janus or gemini? Am J Hum Genet. 1998 Aug;63(2):317–321. doi: 10.1086/301992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Maul G. G., Yu E., Ishov A. M., Epstein A. L. Nuclear domain 10 (ND10) associated proteins are also present in nuclear bodies and redistribute to hundreds of nuclear sites after stress. J Cell Biochem. 1995 Dec;59(4):498–513. doi: 10.1002/jcb.240590410. [DOI] [PubMed] [Google Scholar]
  49. Mu Z. M., Chin K. V., Liu J. H., Lozano G., Chang K. S. PML, a growth suppressor disrupted in acute promyelocytic leukemia. Mol Cell Biol. 1994 Oct;14(10):6858–6867. doi: 10.1128/mcb.14.10.6858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Mu Z. M., Le X. F., Vallian S., Glassman A. B., Chang K. S. Stable overexpression of PML alters regulation of cell cycle progression in HeLa cells. Carcinogenesis. 1997 Nov;18(11):2063–2069. doi: 10.1093/carcin/18.11.2063. [DOI] [PubMed] [Google Scholar]
  51. Müller S., Matunis M. J., Dejean A. Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus. EMBO J. 1998 Jan 2;17(1):61–70. doi: 10.1093/emboj/17.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Nickerson J. A., Blencowe B. J., Penman S. The architectural organization of nuclear metabolism. Int Rev Cytol. 1995;162A:67–123. doi: 10.1016/s0074-7696(08)61229-2. [DOI] [PubMed] [Google Scholar]
  53. Onodera M., Kunisada T., Nishikawa S., Sakiyama Y., Matsumoto S., Nishikawa S. Overexpression of retinoic acid receptor alpha suppresses myeloid cell differentiation at the promyelocyte stage. Oncogene. 1995 Oct 5;11(7):1291–1298. [PubMed] [Google Scholar]
  54. Pandolfi P. P. PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia. Haematologica. 1996 Sep-Oct;81(5):472–482. [PubMed] [Google Scholar]
  55. Saurin A. J., Borden K. L., Boddy M. N., Freemont P. S. Does this have a familiar RING? Trends Biochem Sci. 1996 Jun;21(6):208–214. [PubMed] [Google Scholar]
  56. Scheer U., Weisenberger D. The nucleolus. Curr Opin Cell Biol. 1994 Jun;6(3):354–359. doi: 10.1016/0955-0674(94)90026-4. [DOI] [PubMed] [Google Scholar]
  57. Shiama N. The p300/CBP family: integrating signals with transcription factors and chromatin. Trends Cell Biol. 1997 Jun;7(6):230–236. doi: 10.1016/S0962-8924(97)01048-9. [DOI] [PubMed] [Google Scholar]
  58. Skinner P. J., Koshy B. T., Cummings C. J., Klement I. A., Helin K., Servadio A., Zoghbi H. Y., Orr H. T. Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures. Nature. 1997 Oct 30;389(6654):971–974. doi: 10.1038/40153. [DOI] [PubMed] [Google Scholar]
  59. Sternsdorf T., Grötzinger T., Jensen K., Will H. Nuclear dots: actors on many stages. Immunobiology. 1997 Dec;198(1-3):307–331. doi: 10.1016/S0171-2985(97)80051-4. [DOI] [PubMed] [Google Scholar]
  60. Takahashi M., Inaguma Y., Hiai H., Hirose F. Developmentally regulated expression of a human "finger"-containing gene encoded by the 5' half of the ret transforming gene. Mol Cell Biol. 1988 Apr;8(4):1853–1856. doi: 10.1128/mcb.8.4.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Terris B., Baldin V., Dubois S., Degott C., Flejou J. F., Hénin D., Dejean A. PML nuclear bodies are general targets for inflammation and cell proliferation. Cancer Res. 1995 Apr 1;55(7):1590–1597. [PubMed] [Google Scholar]
  62. Tsai S., Collins S. J. A dominant negative retinoic acid receptor blocks neutrophil differentiation at the promyelocyte stage. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7153–7157. doi: 10.1073/pnas.90.15.7153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wang Z. G., Delva L., Gaboli M., Rivi R., Giorgio M., Cordon-Cardo C., Grosveld F., Pandolfi P. P. Role of PML in cell growth and the retinoic acid pathway. Science. 1998 Mar 6;279(5356):1547–1551. doi: 10.1126/science.279.5356.1547. [DOI] [PubMed] [Google Scholar]
  64. Weis K., Rambaud S., Lavau C., Jansen J., Carvalho T., Carmo-Fonseca M., Lamond A., Dejean A. Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells. Cell. 1994 Jan 28;76(2):345–356. doi: 10.1016/0092-8674(94)90341-7. [DOI] [PubMed] [Google Scholar]
  65. Wells R. A., Catzavelos C., Kamel-Reid S. Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Nat Genet. 1997 Sep;17(1):109–113. doi: 10.1038/ng0997-109. [DOI] [PubMed] [Google Scholar]
  66. Zhu J., Koken M. H., Quignon F., Chelbi-Alix M. K., Degos L., Wang Z. Y., Chen Z., de Thé H. Arsenic-induced PML targeting onto nuclear bodies: implications for the treatment of acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3978–3983. doi: 10.1073/pnas.94.8.3978. [DOI] [PMC free article] [PubMed] [Google Scholar]

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