Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Role and fate of PML nuclear bodies in response to interferon and viral infections

Oncogene volume 20, pages 7274–7286 (2001)Cite this article

Abstract

Interferons (IFNs) are a family of secreted proteins with antiviral, antiproliferative and immunomodulatory activities. The different biological actions of IFN are believed to be mediated by the products of specifically induced cellular genes in the target cells. The promyelocytic leukaemia (PML) protein localizes both in the nucleoplasm and in matrix-associated multi-protein complexes known as nuclear bodies (NBs). PML is essential for the proper formation and the integrity of the NBs. Modification of PML by the Small Ubiquitin MOdifier (SUMO) was shown to be required for its localization in NBs. The number and the intensity of PML NBs increase in response to interferon (IFN). Inactivation of the IFN-induced PML gene by its fusion to retinoic acid receptor alpha alters the normal localization of PML from the punctuate nuclear patterns of NBs to micro-dispersed tiny dots and results in uncontrolled growth in Acute Promyelocytic Leukaemia. The NBs-associated proteins, PML, Sp100, Sp140, Sp110, ISG20 and PA28 are induced by IFN suggesting that nuclear bodies could play a role in IFN response. Although the function of PML NBs is still unclear, some results indicate that they may represent preferential targets for viral infections and that PML could play a role in the mechanism of the antiviral action of IFNs. Viruses, which require the cellular machinery for their replication, have evolved different ways to counteract the action of IFN by inhibiting IFN signalling, by blocking the activities of specific antiviral mediators or by altering PML expression and/or localization on nuclear bodies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

Abbreviations

PML:

pro-myelocytic leukaemia

APL:

acute promyelocytic leukaemia

SUMO:

Small Ubiquitin MOdifier

PKR:

protein kinase RNA-dependent

IRF:

interferon regulatory factor

IFN:

interferon

ISGs:

IFN-stimulated genes

STATs:

signal transducers and activators of transcription

NBs:

nuclear bodies

ISRE:

IFN-stimulated response element

GAS:

IFNγ- activated site

ISGF3:

IFN-stimulated gene factor 3

IFNAR1:

IFN-α receptor1

IFNAR2:

IFN-α receptor2

IFNGR1:

IFN-γ receptor1

IFNGR2:

IFN-γ receptor2

EMCV:

encephalomyocarditis

VSV:

vesicular stomatitis virus

HSV:

herpes simplex virus

LCMV:

lymphocytic choriomeningitis virus

HTLV-1:

human T cell leukaemia virus type1

HDV:

hepatitis delta virus

Tas:

transactivator of spumaviruses

HFV:

human foamy virus

HCV:

hepatitis C virus

HPV:

human papilloma virus

HCMV:

human cytomegalovirus

HCV:

hepatitis C virus

LTR:

long terminal repeats

IP:

internal promoter

References

  • Adelson M, Martinand-Mari C, Iacono K, Muto N, Suhadolnik R . 1999 Eur. J. Biochem. 264: 806–815

  • Ahn JH, Hayward GS . 2000 Virology 274: 39–55

  • Ahn JH, Brignole EJ, Hayward GS . 1998 Mol. Cell. Biol. 18: 4899–4913

  • Ahn JH, Jang WJ, Hayward GS . 1999 J Virol. 73: 10458–10471

  • Alcalay M, Zangrilli D, Fagioli M, Pandolfi PP, Mencarelli A, Lo Coco F, Biondi A, Grignani F, Pelicci PG . 1992 Proc. Natl. Acad. Sci. USA 89: 4840–4844

  • Arnheiter H, Meier E . 1990 New Biol. 2: 851–857

  • Asano K, Merrick W, Hershey J . 1997 J. Biol. Chem. 272: 23477–23480

  • Barnard P, McMillan NA . 1999 Virology 259: 305–313

  • Bell P, Brazas R, Ganem D, Maul G . 2000a J. Virol. 74: 5329–5336

  • Bell P, Lieberman PM, Maul GG . 2000b J. Virol. 74: 11800–11810

  • Bergmann M, Garcia-Sastre A, Carnero E, Pehamberger H, Wolff K, Palese P, Muster T . 2000 J. Virol. 74: 6203–6206

  • Black T, Safer B, Hovanessian A, MG K . 1989 J. Virol. 63: 2244–2251

  • Bloch D, Chiche J, Orth D, de la Monte SM, Rosenzweig A, Bloch K . 1999 Mol. Cell. Biol. 19: 4423–4430

  • Bloch DB, de la Monte SM, Guigaouri P, Filippov A, Bloch KD . 1996 J. Biol. Chem. 271: 29198–29204

  • Bloch DB, Nakajima A, Gulick T, Chiche JD, Orth D, de La Monte SM, Bloch KD . 2000 Mol. Cell. Biol. 20: 6138–6446

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

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

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

  • Borden KLB, Salvato MS . 1998b J. Virol. 72: 758–766

  • Burysek L, Pitha PM . 2001 J. Virol. 75: 2345–2352

  • Burysek L, Yeow W, Lubyova B, Kellum M, Schafer S, Huang Y, Pitha P . 1999 J. Virol. 73: 7334–7342

  • Cai R, Carpick B, Chun R, Jeang K, Willams B . 2000 Arch. Biochem. Biophys. 373: 361–367

  • Campbell Dwyer E, Lai H, MacDonald R, Salvato M, Borden K . 2000 J. Virol. 74: 3293–3300

  • Carvalho T, Seeler J, Ohman K, Jordan P, Petterson U, Akusjarvi G, Carmo-Fonseca M, Dejean A . 1995 J. Biol. Cell. 131: 45–56

  • Cayley PJ, Davies JA, McCullagh KG, Kerr IM . 1984 Eur. J. Biochem. 143: 165–174

  • Chebath J, Benech P, Revel M, Vigneron M . 1987 Nature 330: 587–588

  • Chelbi-Alix M, de Thé H . 1999 Oncogene 18: 935–941

  • Chelbi-Alix MK, Pelicano L . 1999 Leukemia 13: 1167–1174

  • Chelbi-Alix MK, Pelicano L, Quignon F, Koken MHM, de Thé H . Regulation of cell growth differentiation and genetics in cancers Tsiftsoglou AS, Sartorelli AC, Housman DE, Dexter MT (ed). Tumor Biology 99: 17–27

  • Chelbi-Alix MK, Pelicano L, Quignon F, Koken MHM, Venturini L, Stadler M, Pavlovic J, Degos L, de Thé H . 1995 Leukemia 9: 2027–2033

  • Chelbi-Alix MK, Quignon F, Pelicano L, Koken MHM, de The H . 1998 J. Virol. 72: 1043–1051

  • Cheng G, Gross M, Brett ME, He B . 2001 J. Virol. 75: 3666–3675

  • Chenik M, Chebli K, Blondel D . 1995 J. Virol. 69: 707–712

  • Coccia EM, Romeo G, Nissim A, Marziali G . 1990 Virology 179: 228–233

  • Daniel MT, Koken M, Romagne O, Barbey S, Bazarbachi A, Stadler M, Guillemin MC, Degos L, Chomienne C, de The H . 1993 Blood 82: 1858–1867

  • Day M, Roden R, Lowy D, Schiller J . 1998 J. Virol. 72: 142–150

  • Dent AL, Yewdell J, Puvion-Dutilleul F, Koken MHM, de Thé H, Staudt LM . 1996 Blood 88: 1423–1436

  • Der S, Zhou A, Williams B, Silverman R . 1998 Proc. Natl. Acad. Sci. 95: 15623–15628

  • Der SD, Lau AS . 1995 Proc. Natl. Acad. Sci. 92: 8841–8845

  • Desbois C, Rousset R, Bantignies F, Jalinot P . 1996 Science 273: 951–953

  • Diaz-Guerra M, Rivas C, Esteban M . 1997 Virology 227: 220–228

  • Djavani M, Rodas J, Lukashevich IS, Horejsh D, Pandolfi PP, Borden KL, Salvato MS . 2001 J. Virol. 75: 6204–6208

  • Dyck JA, Maul GG, Miller Jr WH, Chen JD, Kakizuka A, Evans RM . 1994 Cell 76: 333–343

  • Everett RD . 1999 Trends Biochem. Sci. 24: 293–295

  • Everett RD, Freemont P, Saitoh H, Dasso M, Orr A, Kathoria M, Parkinson J . 1998 J. Virol. 72: 6581–6591

  • Fabunmi RP, Wigley WC, Thomas PJ, DeMartino GN . 2001 J. Cell. Sci. 114: 29–36

  • Foss GS, Prydz H . 1999 J. Biol. Chem. 274: 35196–35202

  • Gale Jr M, Katze MG . 1998 Pharmacol. Ther. 78: 29–46

  • Gale MJJ, Kwieciszewski B, Dossett M, Nakao H, Katze MG . 1999 J. Virol. 73: 6506–6516

  • Gongora C, David G, Pintard L, Tissot C, Hua TD, Dejean A, Mechti N . 1997 J. Biol. Chem. 272: 19457–19463

  • Gongora C, Degols G, Espert L, Hua TD, Mechti N . 2000 Nucleic Acids Res. 28: 2333–2341

  • Goodbourn S, Didcock L, Randall R . 2000 J. Gen. Virol. 81: 2341–2364

  • Grötzinger T, Jensen K, Will H . 1996 J. Biol. Chem. 271: 25253–25260

  • Guldner H, Szostecki C, Grotzinger T, Will H . 1992 J. Immunol. 149: 4067–4073

  • Gunnery S, Rice AP, Robertson HD, Mathews MB . 1990 Proc. Natl. Acad. Sci. 87: 8687–8691

  • Guo J, Sen G . 2000 J. Virol. 74: 1892–1899

  • Haller O, Frese M, Kochs G . 1998 Rev. Sci. Tech. 17: 220–230

  • Hassel B, Zhou A, Sotomayor C, Maran A, Silverman R . 1993 EMBO J. 12: 3297–3304

  • Hatada E, Saito S, Fukuda R . 1999 J. Virol. 73: 2425–2433

  • He F, Blair WS, Fukushima J, Cullen BR . 1996 J. Virol. 70: 3902–3908

  • Heim MH, Moradpour D, Blum HE . 1999 J. Virol. 73: 8469–8475

  • Imani F, Jacobs BL . 1988 Proc. Natl. Acad. Sci. 85: 7887–7891

  • Ishov A, Sotnikov A, Negorev D, Vladimirova O, Neff N, Kamitani T, Yeh E, Strauss III J, Maul G . 1999 J. Cell. Biol. 147: 221–223

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

  • Kumar R, Choubey D, Lengyel P, Sen GC . 1988 J. Virol. 62: 3175–3181

  • Lanotte M, Martin-Thouvenin V, Najman S, Balerini P, Valensi F, Berger R . 1991 Blood. 77: 1080–1086

  • Lavau C, Marchio A, Fagioli M, Jansen J, Falini B, Lebon P, Grosveld F, Pandolfi PP, Pelicci PG, Dejean A . 1995 Oncogene 11: 871–876

  • Lecellier CH, Saib A . 2000 Virology 271: 1–8

  • Leonard G, Sen G . 1997 J. Virol. 71: 5095–5101

  • Li S, Labrecque S, Gauzzi M, Cuddihy A, Wong A, Pellegrini S, Matlashewski G, Koromilas A . 1999 Oncogene 18: 5727–5737

  • Linial ML . 1999 J. Virol. 73: 1747–1755

  • Look D, Roswit W, Frick A, Gris-alevy Y, Dickhaus D, Walter D, Holtzman M . 1998 Immunity 9: 871–880

  • Marchetti A, Buttitta F, Miyazaki S, Gallahan D, Smith G, Callahan R . 1995 J. Virol. 69: 1932–1938

  • Martinand C, Montavon C, Salehzada T, Silhol M, Lebleu B, Bisbal C . 1999 J. Virol. 73: 290–296

  • Maul G, Everett R . 1994 J. Gen. Virol. 75: 1223–1233

  • Meier E, Fäh J, Grob MS, End R, Staeheli P, Haller O . 1988 J. Virol. 62: 2386–2393

  • Melville MW, Tan SL, Wambach M, Song J, Morimoto RI, Katze MG . 1999 J. Biol. Chem. 274: 3797–3803

  • Meurs EF, Watanabe Y, Kadereit S, Barber GN, Katze MG, Chong K, Williams BRG, Hovanessian AG . 1992 J. Virol. 66: 5805–5814

  • Meurs EF, McMillan N, William BRG, Hovanessian AG, Southern PJ . 1995 Virology 214: 653–659

  • Miller D, Rahill B, Boss J, Lairmore M, Durbin J, Waldman J, Sedmak D . 1998 J. Exp. Med. 187: 675–683

  • Miller D, Zhang Y, Rahill B, Waldman W, Sedmak D . 1999 J. Immunol. 162: 6107–6113

  • Morris-Desbois C, Bochard V, Reynaud C, Jalinot P . 1999 J. Cell. Sci. 112: 3331–3342

  • Muller S, Dejean A . 1999 J. Virol. 73: 5137–5143

  • Nason-Burchenal K, Gandini D, Botto M, Allopenna J, Seale JRC, Cross NCP, Goldman JM, Dmitrovsky E, Pandolfi PP . 1995 Blood 88: 3926–3936

  • Nguyen L, Espert L, Mechti N, Wilson D . 2001 Biochemistry 40: 7174–7179

  • Pavlovic J, Zurcher T, Haller O, Staeheli P . 1990 J. Virol. 64: 3370–3375

  • Pelicano L, Brumpt C, Pitha PM, Chelbi-Alix MK . 1999 Oncogene 18: 3944–3953

  • Pellegrini S, Dusanter-Fourt I . 1997 Eur. J. Biochem. 248: 615–633

  • Pfeffer LM, Dinarello CA, Herberman RB, Williams BRG, Borden EC, Borden R, Walter MR, Nagabhushan TL, Trotta PP, Pestka S . 1998 Cancer Res. 58: 2489–2499

  • Pine R, Canova A, Schindler C . 1994 EMBO J. 13: 158–167

  • Player MR, Torrence PF . 1998 Pharmacol. Ther. 78: 55–113

  • Poppers J, Mulvey M, Khoo D, Mohr I . 2000 J. Virol. 74: 11215–11221

  • Puvion-Dutilleul F, Chelbi-Alix M, Koken M, Quignon F, Puvion E, de The H . 1995 Exp. Cell. Res. 218: 9–16

  • Puvion-Dutilleul F, Legrand V, Mehtali M, Chelbi-Alix MK, de Thé H, Puvion E . 1999 Biol. Cell 91: 617–628

  • Rechsteiner M, Realini C, Ustrell V . 2000 Biochem. J. 345: 1–15

  • Regad T, Saib A, Lallemand-Breitenbach V, Pondolfi PP, de The H, Chelbi-Alix MK . 2001 EMBO J. 20: 3495–3505

  • Schindler C, Darnell JEJ . 1995 Annu. Rev. Biochem. 64: 621–651

  • Schroder H, Ugarkovic D, Merz H, Okamoto T, Muller W . 1990 FASEB J. 4: 3124–3130

  • Sen GC, Ransohoff RM . 1993 Adv. Virus Res. 42: 57–102

  • Sharp T, Schwemmle M, Jeffrey I, Laing K, Mellor H, Proud G, Hilse K, Clemens M . 1993 Nucleic Acids Res. 21: 4483–4490

  • Sharp TV, Moonan F, Romashko A, Joshi B, Barber GN, Jagus R . 1998 Virology 250: 302–315

  • Sharp TV, Witzel JE, Jagus R . 1997 Eur. J. Biochem. 250: 85–91

  • Stadler M, Chelbi-Alix MK, Koken MHM, Venturini L, Lee C, Saïb A, Quignon F, Pelicano L, Guillemin M-C, Schindler C, de Thé H . 1995 Oncogene 11: 2565–2573

  • Staeheli P, Pitossi F, Pavlovic J . 1993 Trends Cell. Biol. 3: 268–272

  • Stark GR, Kerr IM, William BRG, Silverman RH, Schreiber RD . 1998 Annu. Rev. Biochem. 67: 227–264

  • Sternsdorf T, Grotzinger T, Jensen K, Will H . 1997 Immunobiology 198: 307–331

  • Szekely L, Pokrovskaja K, Jiang W, de The H, Ringertz N, Klein G . 1996 J. Virol. 70: 2562–2568

  • Tanahashi N, Yokota K, Ahn J, Chung C, Fujiwara T, Takahashi E, DeMartino G, Slaughter C, Toyonaga T, Yamamura K, Shimbara N, Tanaka K . 1997 Genes Cells 2: 195–211

  • Taylor DR, Shi ST, Romano PR, Barber GN, Lai MM . 1999 Science 285: 107–110

  • Testa U, Grignani F, Barberi T, Fagioli M, Masciulli R, Ferrucci PF, Seripa D, Camagna A, Alcalay M, Pelicci PG, Peschle C . 1994 Cancer Res. 54: 4508–4515

  • Wang ZG, Ruggero D, Ronchetti S, Zhong S, Gaboli M, Rivi R, Pandolfi PP . 1998a Nature Genet. 20: 266–272

  • Wang ZG, Delva L, Gaboli M, Rivi R, Giorgio M, Cordon-Cardo C, Grosveld F, Pandolfi PP . 1998b Science 279: 1547–1551

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

  • Yang YL, Reis LF, Pavlovic J, Aguzzi A, Schafer R, Kumar A, Williams BR, Aguet M, Weissmann C . 1995 EMBO J. 14: 6095–6106

  • Zhou A, Paranjape J, Brown TL, Nie H, Naik S, Dong B, Chang A, Trapp B, Fairchild R, Colmenares C, Silverman RH . 1997 EMBO J. 16: 6355–6363

  • Zhou A, Paranjape J, Der S, Williams B, Silverman R . 1999 Virology 258: 435–440

  • Zimring J, Goodbourn S, Offermann M . 1998 J. Virol 701–707

  • Zürcher T, Pavlovic J, Staeheli P . 1992a Virology 187: 796–800

  • Zürcher T, Pavlovic J, Staeheli P . 1992b J. Virol. 66: 5059–5066

Download references

Acknowledgements

We thank Roger Everett and all our colleagues from UPR 9045 of Centre National pour la Recherche Scientifique for comments on the manuscript. This work was supported by grants from CNRS and Association pour la Recherche sur le Cancer.

Author information

Authors and Affiliations

  1. UPR 9045 CNRS, Institut André Lwoff, 7 rue Guy Moquet, Villejuif, Cedex, 94801, France

    Tarik Regad & Mounira K Chelbi-Alix

Authors
  1. Tarik Regad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mounira K Chelbi-Alix
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mounira K Chelbi-Alix.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Regad, T., Chelbi-Alix, M. Role and fate of PML nuclear bodies in response to interferon and viral infections. Oncogene 20, 7274–7286 (2001). https://doi.org/10.1038/sj.onc.1204854

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204854

Keywords

This article is cited by

Search

Advanced search

Quick links