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:

PML protein isoforms and the RBCC/TRIM motif

Oncogene volume 20, pages 7223–7233 (2001)Cite this article

Abstract

PML is a component of a multiprotein complex, termed nuclear bodies, and the PML protein was originally discovered in patients suffering from acute promyelocytic leukaemia (APL). APL is associated with a reciprocal chromosomal translocation of chromosomes 15 and 17, which results in a fusion protein comprising PML and the retinoic acid receptor α. The PML genomic locus is approximately 35 kb and is subdivided into nine exons. A large number of alternative spliced transcripts are synthesized from the PML gene, resulting in a variety of PML proteins ranging in molecular weight from 48–97 kDa. In this review we summarize the data on the known PML isoforms and splice variants and present a new unifying nomenclature. Although, the function/s of the PML variants are unclear, all PML isoforms contain an identical N-terminal region, suggesting that these sequences are indispensable for function, but differ in their C-terminal sequences. The N-terminal region harbours a RING-finger, two B-boxes and a predicted α-helical Coiled-Coil domain, that together form the RBCC/TRIM motif found in a large family of proteins. In PML this motif is essential for PML nuclear body formation in vivo and PML-homo and hetero interactions conferring growth suppressor, apoptotic and anti-viral activities. In APL oligomerization mediated by the RBCC/TRIM motif is essential for the transformation potential of the PML-RARα fusion protein.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • 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

References

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

  • Ahn MJ, Nason-Burchenal K, Moasser MM, Dmitrovsky E . 1995 Oncogene 10: 2307–2314

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

  • 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

  • Altabef M, Garcia M, Lavau C, Bae SC, Dejean A, Samarut J . 1996 EMBO J. 15: 2707–2716

  • Ascoli CA, Maul GG . 1991 J. Cell. Biol. 112: 785–795

  • Avela K, Lipsanen-Nyman M, Idanheimo N, Seemanova E, Rosengren S, Makela TP, Perheentupa J, Chapelle A, Lehesjoki AE . 2000 Nat. Genet. 25: 298–301

  • Bellini M, Lacroix JC, Gall JG . 1993 EMBO J. 12: 107–114

  • Bellini M, Lacroix JC, Gall JG . 1995 J. Cell. Biol. 131: 563–570

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

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

  • Borden KL . 1998 Biochem. Cell. Biol. 76: 351–358

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

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

  • Borden KL, Campbelldwyer EJ, Carlile GW, Djavani M, Salvato MS . 1998b J. Virol. 72: 3819–3826

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

  • Borden KL, Lally JM, Martin SR, O'Reilly NJ, Etkin LD, Freemont PS . 1995b EMBO J. 14: 5947–5956

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

  • Brasch K, Ochs RL . 1992 Exp. Cell. Res. 202: 211–223

  • Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG, Atwater S, Bishop JM . 1997 Proc. Natl. Acad. Sci. USA 94: 2551–2556

  • Buchner G, Montini E, Andolfi G, Quaderi N, Cainarca S, Messali S, Bassi MT, Ballabio A, Meroni G, Franco B . 1999 Hum. Mol. Genet. 8: 1397–1407

  • Cainarca S, Messali S, Ballabio A, Meroni G . 1999 Hum. Mol. Genet. 8: 1387–1396

  • Cao T, Borden KL, Freemont PS, Etkin LD . 1997 J. Cell. Sci. 110: 1563–1571

  • Cao T, Duprez E, Borden KL, Freemont PS, Etkin LD . 1998 J. Cell. Sci. 111: 1319–1329

  • Chan EK, Hamel JC, Buyon JP, Tan EM . 1991 J. Clin. Invest. 87: 68–76

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

  • Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z . 1996 Blood 88: 1052–1061

  • Chu TW, Capossela A, Coleman R, Goei VL, Nallur G, Gruen JR . 1995 Genomics 29: 229–239

  • Cox TC, Allen LR, Cox LL, Hopwood B, Goodwin B, Haan E, Suthers GK . 2000 Hum. Mol. Genet. 9: 2553–2562

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

  • de Thé H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A . 1991 Cell 66: 675–684

  • Desterro JM, Rodriguez MS, Hay RT . 1998 Mol. Cell 2: 233–239

  • Doucas V, Tini M, Egan DA, Evans RM . 1999 Proc. Natl. Acad. Sci. USA 96: 2627–2632

  • Duprez E, Saurin AJ, Desterro JM, Lallemand-Breitenbach V, Howe K, Boddy MN, Solomon E, de Thé H, Hay RT, Freemont PS . 1999 J. Cell. Sci. 112: 381–393

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

  • El-Husseini AE, Fretier P, Vincent SR . 2001 Genomics 71: 363–367

  • El-Husseini AE, Kwasnicka D, Yamada T, Hirohashi S, Vincent SR . 2000 Biochem. Biophys. Res. Commun. 267: 906–911

  • El-Husseini AE, Vincent SR . 1999 J. Biol. Chem. 274: 19771–19777

  • Everett RD, Orr A, Preston CM . 1998 EMBO J. 17: 7161–7169

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

  • Fagioli M, Alcalay M, Tomassoni L, Ferrucci PF, Mencarelli A, Riganelli D, Grignani F, Pozzan T, Nicoletti I, Pelicci PG . 1998 Oncogene 16: 2905–2913

  • Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, Pandolfi PP, Will H, Schneider C, Del Sal G . 2000 EMBO J. 19: 6185–6195

  • Freemont PS . 1993 Ann. N. Y. Acad. Sci. 684: 174–192

  • Freemont PS . 2000 Curr. Biol. 10: R84-R87

  • Fridell RA, Harding LS, Bogerd HP, Cullen BR . 1995 Virology 209: 347–357

  • Friedman JR, Fredericks WJ, Jensen DE, Speicher DW, Huang XP, Neilson EG, Rauscher III FJ . 1996 Genes Dev. 10: 2067–2078

  • Goddard AD, Borrow J, Freemont PS, Solomon E . 1991 Science 254: 1371–1374

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

  • Grignani F, Gelmetti V, Fanelli M, Rogaia D, De Matteis S, Ferrara FF, Bonci D, Nervi C, Pelicci PG . 1999 Oncogene 18: 6313–6321

  • Grignani F, Testa U, Rogaia D, Ferrucci PF, Samoggia P, Pinto A, Aldinucci D, Gelmetti V, Fagioli M, Alcalay M, Seeler J, Nicoletti I, Peschle C, Pelicci PG . 1996 EMBO J. 15: 4949–4958

  • Grisolano JL, Wesselschmidt RL, Pelicci PG, Ley TJ . 1997 Blood 89: 376–387

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

  • Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Paolo Pandolfi P . 2000 Nat. Cell. Biol. 2: 730–736

  • Harada H, Harada Y, O'Brien DP, Rice DS, Naeve CW, Downing JR . 1999 Mol. Cell. Biol. 19: 3808–3815

  • Hasegawa N, Iwashita T, Asai N, Murakami H, Iwata Y, Isomura T, Goto H, Hayakawa T, Takahashi M . 1996 Biochem. Biophys. Res. Commun. 225: 627–631

  • Hodges M, Tissot C, Howe K, Grimwade D, Freemont PS . 1998 Am. J. Hum. Genet. 63: 297–304

  • Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY . 1988 Blood 72: 567–572

  • Inoue S, Orimo A, Hosoi T, Kondo S, Toyoshima H, Kondo T, Ikegami A, Ouchi Y, Orimo H, Muramatsu M . 1993 Proc. Natl. Acad. Sci. USA 90: 11117–11121

  • Inoue S, Urano T, Ogawa S, Saito T, Orimo A, Hosoi T, Ouchi Y, Muramatsu M . 1999 Biochem. Biophys. Res. Commun. 261: 412–418

  • Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss III JF, Maul GG . 1999 J. Cell. Biol. 147: 221–234

  • Jacobson RH, Ladurner AG, King DS, Tjian R . 2000 Science 288: 1422–1425

  • Kakizuka A, Miller WH, Umesono K, Warrell RP, Frankel SR, Murty VV, Dmitrovsky E, Evans RM . 1991 Cell. 66: 663–674

  • Kamitani T, Kito K, Nguyen HP, Wada H, Fukuda-Kamitani T, Yeh ET . 1998b J. Biol. Chem. 273: 26675–26682

  • Kamitani T, Nguyen HP, Kito K, Fukuda-Kamitani T, Yeh ET . 1998a J. Biol. Chem. 273: 3117–3120

  • Kapanadze B, Kashuba V, Baranova A, Rasool O, van Everdink W, Liu Y, Syomov A, Corcoran M, Poltaraus A, Brodyansky V, Syomova N, Kazakov A, Ibbotson R, van den Berg A, Gizatullin R, Fedorova L, Sulimova G, Zelenin A, Deaven L, Lehrach H, Grander D, Buys C, Oscier D, Zabarovsky ER, Einhorn S, Yankovsky N . 1998 FEBS Lett. 426: 266–270

  • Kastner P, Perez A, Lutz Y, Rochette-Egly C, Gaub MP, Durand B, Lanotte M, Berger R, Chambon P . 1992 EMBO J. 11: 629–642

  • Kentsis A, Borden KLB . 2000 Current Protein and Peptide Science 1: 1–25

  • Kim SS, Chen YM, O'Leary E, Witzgall R, Vidal M, Bonventre JV . 1996 Proc. Natl. Acad. Sci. USA 93: 15299–15304

  • Klugbauer S, Rabes HM . 1999 Oncogene 18: 4388–4393

  • Koken MH, Linares-Cruz G, Quignon F, Viron A, Chelbi-Alix MK, Sobczak-Thépot J, Juhlin L, Degos L, Calvo F, de Thé H . 1995 Oncogene 10: 1315–1324

  • Koken MH, 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

  • Lai HK, Borden KL . 2000 Oncogene 19: 1623–1634

  • Lallemand-Breitenbach V, Zhu J, Puvion F, Koken M, Honore N, Doubeikovsky E, Duprez E, Pandolfi P, Puvion E, Freemont PS, de Thé H . 2001 J. Exp. Medicine 193: 1361–1371

  • 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

  • Le Douarin B, Zechel C, Garnier JM, Lutz Y, Tora L, Pierrat P, Heery D, Gronemeyer H, Chambon P, Losson R . 1995 EMBO J. 14: 2020–2033

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

  • Li H, Leo C, Zhu J, Wu X, O'Neil J, Park EJ, Chen JD . 2000 Mol. Cell. Biol. 20: 1784–1796

  • Li YP, Andersen J, Zelent A, Rao S, Paietta E, Tallman MS, Wiernik PH, Gallagher RE . 1997 Blood 90: 306–312

  • Lupas A . 1996 Trends Biochem. Sci. 21: 375–382

  • Mahajan R, Delphin C, Guan T, Gerace L, Melchior F . 1997 Cell. 88: 97–107

  • Matunis MJ, Coutavas E, Blobel G . 1996 J. Cell. Biol. 135: 1457–1470

  • Mishima K, Tsuchiya M, Nightingale MS, Moss J, Vaughan M . 1993 J. Biol. Chem. 268: 8801–8807

  • Moosmann P, Georgiev O, Le Douarin B, Bourquin JP, Schaffner W . 1996 Nucleic Acids Res. 24: 4859–4867

  • Mu ZM, Chin KV, Liu JH, Lozano G, Chang KS . 1994 Mol. Cell. Biol. 14: 6858–6867

  • Muller S, Matunis MJ, Dejean A . 1998 EMBO J. 17: 61–70

  • Nervi C, Ferrara FF, Fanelli M, Rippo MR, Tomassini B, Ferrucci PF, Ruthardt M, Gelmetti V, Gambacorti-Passerini C, Diverio D, Grignani F, Pelicci PG, Testi R . 1998 Blood 92: 2244–2251

  • Ogawa S, Goto W, Orimo A, Hosoi T, Ouchi Y, Muramatsu M, Inoue S . 1998 Biochem. Biophys. Res. Commun. 251: 515–519

  • Orimo A, Tominaga N, Yoshimura K, Yamauchi Y, Nomura M, Sato M, Nogi Y, Suzuki M, Suzuki H, Ikeda K, Inoue S, Muramatsu M . 2000a Genomics 69: 143–149

  • Orimo A, Yamagishi T, Tominaga N, Yamauchi Y, Hishinuma T, Okada K, Suzuki M, Sato M, Nogi Y, Suzuki H, Inoue S, Yoshimura K, Shimizu Y, Muramatsu M . 2000b Biochem. Biophys. Res. Commun. 276: 45–51

  • Palmer S, Perry J, Kipling D, Ashworth A . 1997 Proc. Natl. Acad. Sci. USA 94: 12030–12035

  • Pandolfi PP, Grignani F, Alcalay M, Mencarelli A, Biondi A, LoCoco F, Pelicci PG . 1991 Oncogene 6: 1285–1292

  • Patarca R, Freeman GJ, Schwartz J, Singh RP, Kong QT, Murphy E, Anderson Y, Sheng FY, Singh P, Johnson KA, Guarnagia SM, Durfee T, Blattner F, Cantor H . 1988 Proc. Natl. Acad. Sci. USA 85: 2733–2737

  • Peng H, Begg GE, Schultz DC, Friedman JR, Jensen DE, Speicher DW, Rauscher III FJ . 2000 J. Mol. Biol. 295: 1139–1162

  • Perez A, Kastner P, Sethi S, Lutz Y, Reibel C, Chambon P . 1993 EMBO J. 12: 3171–3182

  • Perrin K, Lacroix JC . 1998 Gene. 210: 127–134

  • Perry J, Short KM, Romer JT, Swift S, Cox TC, Ashworth A . 1999 Genomics 62: 385–394

  • Pollock JL, Westervelt P, Kurichety AK, Pelicci PG, Grisolano JL, Ley TJ . 1999 Proc. Natl. Acad. Sci. USA 96: 15103–15108

  • Quaderi NA, Schweiger S, Gaudenz K, Franco B, Rugarli EI, Berger W, Feldman GJ, Volta M, Andolfi G, Gilgenkrantz S, Marion RW, Hennekam RC, Optiz JM, Muenke M, Ropers HH, Ballabio A . 1997 Nat. Genet. 17: 285–291

  • Quignon F, De Bels F, Koken M, Feunteun J, Ameisen JC, de Thé H . 1998 Nat. Genet. 20: 259–265

  • Raska I, Dundr M, Koberna K . 1992 Cell. Biol. Int. Rep. 16: 771–789

  • Reddy BA, Etkin LD, Freemont PS . 1992 Trends Biochem. Sci. 17: 344–345

  • Reddy BA, Kloc M, Etkin L . 1991 Dev. Biol. 148: 107–116

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

  • Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A . 2001 EMBO J. 20: 2140–2151

  • Saha V, Young BD, Freemont PS . 1998 J. Cell. Biochem. Suppl. 31: 264–276

  • Saitoh H, Pu RT, Dasso M . 1997 Trends Biochem. Sci. 22: 374–376

  • Saurin AJ, Borden KL, Boddy MN, Freemont PS . 1996 Trends Biochem. Sci. 21: 208–214

  • Seeler JS, Dejean A . 1999 Curr. Opin. Genet. Dev. 9: 362–367

  • Shimono Y, Murakami H, Hasegawa Y, Takahashi M . 2000 J. Biol. Chem. 275: 39411–39419

  • Shou W, Li X, Wu C, Cao T, Kuang J, Che S, Etkin LD . 1996 Mol. Cell. Biol. 16: 990–997

  • Slack FJ, Basson M, Liu Z, Ambros V, Horvitz HR, Ruvkun G . 2000 Mol. Cell. 5: 659–669

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

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

  • Sternsdorf T, Jensen K, Will H . 1997b J. Cell. Biol. 139: 1621–1634

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

  • Takahashi M, Inaguma Y, Hiai H, Hirose F . 1988 Mol. Cell. Biol. 8: 1853–1856

  • Tissot C, Mechti N . 1995 J. Biol. Chem. 270: 14891–14898

  • Tissot C, Taviaux SA, Diriong S, Mechti N . 1996 Genomics 34: 151–153

  • Topcu Z, Mack DL, Hromas RA, Borden KL . 1999 Oncogene 18: 7091–7100

  • Tsuzuki S, Towatari M, Saito H, Enver T . 2000 Mol. Cell. Biol. 20: 6276–6286

  • Vallian S, Chin KV, Chang KS . 1998a Mol. Cell. Biol. 18: 7147–7156

  • Vallian S, Gaken JA, Gingold EB, Kouzarides T, Chang KS, Farzaneh F . 1998b Oncogene 16: 2843–2853

  • Venturini L, You J, Stadler M, Galien R, Lallemand V, Koken MH, Mattei MG, Ganser A, Chambon P, Losson R, de Thé H . 1999 Oncogene 18: 1209–1217

  • Vincent SR, Kwasnicka DA, Fretier P . 2000 Biochem. Biophys. Res. Commun. 279: 482–486

  • Vitale N, Moss J, Vaughan M . 1996 Proc. Natl. Acad. Sci. USA 93: 1941–1944

  • Vitale N, Moss J, Vaughan M . 1998 J. Biol. Chem. 273: 2553–2560

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

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

  • Wu WS, Vallian S, Seto E, Yang WM, Edmondson D, Roth S, Chang KS . 2001 Mol. Cell. Biol. 21: 2259–2268

  • Zhong S, Delva L, Rachez C, Cenciarelli C, Gandini D, Zhang H, Kalantry S, Freedman LP, Pandolfi PP . 1999 Nat. Genet. 23: 287–295

  • Zhong S, Salomoni P, Pandolfi PP . 2000 Nat. Cell. Biol. 2: E85–E90

  • Zhu J, Koken MH, Quignon F, Chelbi-Alix MK, Degos L, Wang ZY, Chen Z, de Thé H . 1997 Proc. Natl. Acad. Sci. USA 94: 3978–3983

Download references

Acknowledgements

We thank Kathy Borden and Thomas Sternsdorf for critical reading of the manuscript and helpful discussions. We also thank all our colleagues for contributing to the proposed nomenclature for the PML isoforms.

Author information

Authors and Affiliations

  1. Centre for Structural Biology, Imperial College of Science, Technology and Medicine, Flowers Building, Armstrong Road, London, SW7 2AZ, UK

    Kirsten Jensen, Carol Shiels & Paul S Freemont

Authors
  1. Kirsten Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carol Shiels
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul S Freemont
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul S Freemont.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jensen, K., Shiels, C. & Freemont, P. PML protein isoforms and the RBCC/TRIM motif. Oncogene 20, 7223–7233 (2001). https://doi.org/10.1038/sj.onc.1204765

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204765

Keywords

This article is cited by

Search

Advanced search

Quick links