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:

AP-1 in mouse development and tumorigenesis

Abstract

Genetically modified mice have provided important insights into the biological functions of the dimeric transcription factor complex AP-1. Extensive analyses of mice and cells with genetically modified Fos or Jun proteins provide novel insights into the physiological functions of AP-1 proteins. Using knock-out strategies it was found that some components, such as c-Fos, FosB and JunD are dispensable, whereas others, like c-Jun, JunB and Fra-1 are essential in embryonic development and/or in the adult organism. Besides the specific roles of AP-1 proteins in developmental processes, we are beginning to obtain a better molecular understanding of the cell-context dependent function of AP-1 in cell proliferation and apoptosis, in bone biology as well as in multistep tumorigenesis.

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

Access options

Buy this article

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

Figure 1
Figure 2

Similar content being viewed by others

References

  • Alani R, Brown P, Binetruy B, Dosaka H, Rosenberg RK, Angel P, Karin M, Birrer MJ . 1991 Mol. Cell. Biol. 11: 6286–6295

  • Angel P, Karin M . 1991 Biochim. Biophys. Acta. 1072: 129–157

  • Bakin AV, Curran T . 1999 Science 283: 387–390

  • Bakiri L, Lallemand D, Bossy-Wetzel E, Yaniv M . 2000 EMBO J. 19: 2056–2068

  • Battista S, de Nigris F, Fedele M, Chiappetta G, Scala S, Vallone D, Pierantoni GM, Megar T, Santoro M, Viglietto G, Verde P, Fusco A . 1998 Oncogene 17: 377–385

  • Behrens A, Jochum W, Sibilia M, Wagner EF . 2000 Oncogene 19: 2657–2663

  • Behrens A, Sibilia M, Wagner EF . 1999 Nat. Genet. 21: 326–329

  • Behrens A, Sabapathy K, Graef I, Cleary M, Crabtree GR, Wagner EF . 2001 PNAS in press

  • Bergers G, Graninger P, Braselmann S, Wrighton C, Busslinger M . 1995 Mol. Cell. Biol. 15: 3748–3758

  • Binetruy B, Smeal T, Karin M . 1991 Nature 351: 122–127

  • Bossy-Wetzel E, Bakiri L, Yaniv M . 1997 EMBO J. 16: 1695–1709

  • Brown JR, Nigh E, Lee RJ, Ye H, Thompson MA, Saudou F, Pestell RG, Greenberg ME . 1998 Mol. Cell. Biol. 18: 5609–5619

  • Brown JR, Ye H, Bronson RT, Dikkes P, Greenberg ME . 1996 Cell. 86: 297–309

  • Brown PH, Alani R, Preis LH, Szabo E, Birrer MJ . 1993 Oncogene 8: 877–886

  • Brüsselbach S, Möhle-Steinlein U, Wang ZQ, Schreiber M, Lucibello FC, Müller R, Wagner EF . 1995 Oncogene 10: 79–86

  • Buttyan R, Zakeri Z, Lockshin R, Wolgemuth D . 1988 Mol. Endocrinol. 2: 650–657

  • Carrasco D, Bravo R . 1995 Oncogene 10: 1069–1079

  • Carrozza ML, Jacobs H, Acton D, Verma I, Berns A . 1997 Oncogene 14: 1083–1091

  • Castellazzi M, Spyrou G, La Vista N, Dangy JP, Piu F, Yaniv M, Brun G . 1991 Proc. Natl. Acad. Sci. USA 88: 8890–8894

  • Chen J, Stewart V, Spyrou G, Hilberg F, Wagner EF, Alt FW . 1994 Immunity 1: 65–72

  • Colotta F, Polentarutti N, Sironi M, Mantovani A . 1992 J. Biol. Chem. 267: 18278–18283

  • Cook SJ, Aziz N, McMahon M . 1999 Mol. Cell. Biol. 19: 330–341

  • Curran T, MacConnell WP, van Straaten F, Verma IM . 1983 Mol. Cell. Biol. 3: 914–921

  • Eferl R, Sibilia M, Hilberg F, Fuchsbichler A, Kufferath I, Guertl B, Zenz R, Wagner EF, Zatloukal K . 1999 J. Cell. Biol. 145: 1049–1061

  • Estus S, Zaks WJ, Freeman RS, Gruda M, Bravo R, Johnson Jr EM . 1994 J. Cell. Biol. 127: 1717–1727

  • Feng Z, Joos HJ, Vallan C, Muhlbauer R, Altermatt HJ, Jaggi R . 1998 Oncogene 17: 2593–2600

  • Fialka I, Schwarz H, Reichmann E, Oft M, Busslinger M, Beug H . 1996 J. Cell. Biol. 132: 1115–1132

  • Field SJ, Johnson RS, Mortensen RM, Papaioannou VE, Spiegelman BM, Greenberg ME . 1992 Proc. Natl. Acad. Sci. USA 89: 9306–9310

  • Fleischmann A, Hafezi F, Elliott C, Reme CE, Rüther U, Wagner EF . 2000 Genes Dev. 14: 2695–2700

  • Foletta VC, Sonobe MH, Suzuki T, Endo T, Iba H, Cohen DR . 1994 Oncogene 9: 3305–3311

  • Funk M, Poensgen B, Graulich W, Jerome V, Müller R . 1997 Mol. Cell. Biol. 17: 537–544

  • Gack S, Vallon R, Schaper J, Rüther U, Angel P . 1994 J. Biol. Chem. 269: 10363–10369

  • Gajate C, Alonso MT, Schimmang T, Mollinedo F . 1996 Biochem. Biophys. Res. Commun. 218: 267–272

  • Grigoriadis AE, Schellander K, Wang ZQ, Wagner EF . 1993 J. Cell. Biol. 122: 685–701

  • Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA, Wagner EF . 1994 Science 266: 443–448

  • Gruda MC, van Amsterdam J, Rizzo CA, Durham SK, Lira S, Bravo R . 1996 Oncogene 12: 2177–2185

  • Hafezi F, Steinbach JP, Marti A, Munz K, Wang ZQ, Wagner EF, Aguzzi A, Reme CE . 1997 Nat. Med. 3: 346–349

  • Ham J, Babij C, Whitfield J, Pfarr CM, Lallemand D, Yaniv M, Rubin LL . 1995 Neuron 14: 927–939

  • Hanahan D, Weinberg RA . 2000 Cell. 100: 57–70

  • Hennigan RF, Hawker KL, Ozanne BW . 1994 Oncogene 9: 3591–3600

  • Hilberg F, Aguzzi A, Howells N, Wagner EF . 1993 Nature 365: 179–181

  • Hilberg F, Wagner EF . 1992 Oncogene 7: 2371–2380

  • Hu E, Mueller E, Oliviero S, Papaioannou VE, Johnson R, Spiegelman BM . 1994 EMBO J. 13: 3094–3103

  • Hu L, Hatano M, Rüther U, Tokuhisa T . 1996 J. Immunol. 157: 3804–3811

  • Ivanov VN, Nikolic-Zugic J . 1997 J. Biol. Chem. 272: 8558–8566

  • Jain J, Nalefski EA, McCaffrey PG, Johnson RS, Spiegelman BM, Papaioannou V, Rao A . 1994 Mol. Cell. Biol. 14: 1566–1574

  • Jenuwein T, Müller R . 1987 Cell. 48: 647–657

  • Jochum W, David JP, Elliott C, Wutz A, Plenk Jr H, Matsuo K, Wagner EF . 2000 Nat. Med. 6: 980–984

  • Johnson R, Spiegelman B, Hanahan D, Wisdom R . 1996 Mol. Cell. Biol. 16: 4504–4511

  • Johnson RS, Spiegelman BM, Papaioannou V . 1992 Cell. 71: 577–586

  • Johnson RS, van Lingen B, Papaioannou VE, Spiegelman BM . 1993 Genes Dev. 7: 1309–1317

  • Johnston IM, Spence HJ, Winnie JN, McGarry L, Vass JK, Meagher L, Stapleton G, Ozanne BW . 2000 Oncogene 19: 5348–5358

  • Jooss KU, Funk M, Müller R . 1994 EMBO J. 13: 1467–1475

  • Jooss KU, Müller R . 1995 Oncogene 10: 603–608

  • Kameda T, Akahori A, Sonobe MH, Suzuki T, Endo T, Iba H . 1993 Proc. Natl. Acad. Sci. USA 90: 9369–9373

  • Karsenty G . 1999 Genes Dev. 13: 3037–3051

  • Kolbus A, Herr I, Schreiber M, Debatin KM, Wagner EF, Angel P . 2000 Mol. Cell. Biol. 20: 575–582

  • Kovary K, Bravo R . 1991 Mol. Cell. Biol. 11: 2451–2459

  • Kovary K, Rizzo CA, Ryseck RP, Noguchi T, Raynoschek C, Pelosin JM, Bravo R . 1991 New. Biol. 3: 870–879

  • Kustikova O, Kramerov D, Grigorian M, Berezin V, Bock E, Lukanidin E, Tulchinsky E . 1998 Mol. Cell. Biol. 18: 7095–7105

  • Lallemand D, Spyrou G, Yaniv M, Pfarr CM . 1997 Oncogene 14: 819–830

  • Lamb RF, Hennigan RF, Turnbull K, Katsanakis KD, MacKenzie ED, Birnie GD, Ozanne BW . 1997 Mol. Cell. Biol. 17: 963–976

  • Li B, Tournier C, Davis RJ, Flavell RA . 1999 EMBO J. 18: 420–432

  • Liebermann DA, Gregory B, Hoffman B . 1998 Int. J. Oncol. 12: 685–700

  • Lloyd A, Yancheva N, Wasylyk B . 1991 Nature 352: 635–638

  • Maki Y, Bos TJ, Davis C, Starbuck M, Vogt PK . 1987 Proc. Natl. Acad. Sci. USA 84: 2848–2852

  • Malliri A, Symons M, Hennigan RF, Hurlstone AF, Lamb RF, Wheeler T, Ozanne BW . 1998 J. Cell. Biol. 143: 1087–1099

  • Marconcini L, Marchio S, Morbidelli L, Cartocci E, Albini A, Ziche M, Bussolino F, Oliviero S . 1999 Proc. Natl. Acad. Sci. USA 96: 9671–9676

  • Marti A, Jehn B, Costello E, Keon N, Ke G, Martin F, Jaggi R . 1994 Oncogene 9: 1213–1223

  • Matsuo K, Owens JM, Tonko M, Elliott C, Chambers TJ, Wagner EF . 2000 Nat. Genet. 24: 184–187

  • McCabe LR, Banerjee C, Kundu R, Harrison RJ, Dobner PR, Stein JL, Lian JB, Stein GS . 1996 Endocrinology 137: 4398–4408

  • McHenry JZ, Leon A, Matthaei KI, Cohen DR . 1998 Oncogene 17: 1131–1140

  • Mechta F, Lallemand D, Pfarr CM, Yaniv M . 1997 Oncogene 14: 837–847

  • Miao GG, Curran T . 1994 Mol. Cell. Biol. 14: 4295–4310

  • Miller AD, Curran T, Verma IM . 1984 Cell. 36: 51–60

  • Mumberg D, Lucibello FC, Schuermann M, Müller R . 1991 Genes Dev. 5: 1212–1223

  • Nakabeppu Y, Nathans D . 1991 Cell. 64: 751–759

  • Nishina H, Sato H, Suzuki T, Sato M, Iba H . 1990 Proc. Natl. Acad. Sci. USA 87: 3619–3623

  • Okada S, Wang ZQ, Grigoriadis AE, Wagner EF, von Rüden T . 1994 Mol. Cell. Biol. 14: 382–390

  • Orlandini M, Marconcini L, Ferruzzi R, Oliviero S . 1996 Proc. Natl. Acad. Sci. USA 93: 11675–11680

  • Owens JM, Matsuo K, Nicholson GC, Wagner EF, Chambers TJ . 1999 J. Cell. Physiol. 179: 170–178

  • Passegué E, Wagner EF . 2000 EMBO J. 19: 2969–2979

  • Passegué E, Jochum W, Schorpp-Kistner M, Möhle-Steinlein U, Wagner EF . 2001 Cell. 104: 21–32

  • Pennypacker K . 1998 Int. Rev. Neurobiol. 42: 169–197

  • Pfarr CM, Mechta F, Spyrou G, Lallemand D, Carillo S, Yaniv M . 1994 Cell. 76: 747–760

  • Preston GA, Lyon TT, Yin Y, Lang JE, Solomon G, Annab L, Srinivasan DG, Alcorta DA, Barrett JC . 1996 Mol. Cell. Biol. 16: 211–218

  • Reichmann E, Schwarz H, Deiner EM, Leitner I, Eilers M, Berger J, Busslinger M, Beug H . 1992 Cell. 71: 1103–1116

  • Roffler-Tarlov S, Brown JJ, Tarlov E, Stolarov J, Chapman DL, Alexiou M, Papaioannou VE . 1996 Development 122: 1–9

  • Rüther U, Komitowski D, Schubert FR, Wagner EF . 1989 Oncogene 4: 861–865

  • Sabatakos G, Sims NA, Chen J, Aoki K, Kelz MB, Amling M, Bouali Y, Mukhopadhyay K, Ford K, Nestler EJ, Baron R . 2000 Nat. Med. 6: 985–990

  • Saez E, Oppenheim H, Smoluk J, Andersen JW, Van Etten RA, Spiegelman BM . 1995a Cancer Res. 55: 6196–6199

  • Saez E, Rutberg SE, Mueller E, Oppenheim H, Smoluk J, Yuspa SH, Spiegelman BM . 1995b Cell. 82: 721–732

  • Sandberg M, Vuorio T, Hirvonen H, Alitalo K, Vuorio E . 1988 Development 102: 461–470

  • Schorpp M, Jager R, Schellander K, Schenkel J, Wagner EF, Weiher H, Angel P . 1996 Nucleic Acids. Res. 24: 1787–1788

  • Schorpp-Kistner M, Wang ZQ, Angel P, Wagner EF . 1999 EMBO J. 18: 934–948

  • Schreiber M, Baumann B, Cotten M, Angel P, Wagner EF . 1995 EMBO J. 14: 5338–5349

  • Schreiber M, Kolbus A, Piu F, Szabowski A, Möhle-Steinlein U, Tian J, Karin M, Angel P, Wagner EF . 1999 Genes Dev. 13: 607–619

  • Schreiber M, Wang Z, Jochum W, Fetka I, Elliott C, Wagner EF . 2000 Development 127: 4937–4948

  • Schuermann M, Jooss K, Müller R . 1991 Oncogene 6: 567–576

  • Schuermann M, Neuberg M, Hunter JB, Jenuwein T, Ryseck RP, Bravo R, Müller R . 1989 Cell. 56: 507–516

  • Schuh AC, Keating SJ, Monteclaro FS, Vogt PK, Breitman ML . 1990 Nature 346: 756–760

  • Schütte J, Minna JD, Birrer MJ . 1989a Proc. Natl. Acad. Sci. USA 86: 2257–2261

  • Schütte J, Viallet J, Nau M, Segal S, Fedorko J, Minna J . 1989b Cell. 59: 987–997

  • Shaulian E, Schreiber M, Piu F, Beeche M, Wagner EF, Karin M . 2000 Cell. 103: 897–907

  • Skinner M, Qu S, Moore C, Wisdom R . 1997 Mol. Cell. Biol. 17: 2372–2380

  • Smeal T, Binetruy B, Mercola DA, Birrer M, Karin M . 1991 Nature 354: 494–496

  • Smeyne RJ, Curran T, Morgan JI . 1992a Brain. Res. Mol. Brain. Res. 16: 158–162

  • Smeyne RJ, Schilling K, Robertson L, Luk D, Oberdick J, Curran T, Morgan JI . 1992b Neuron 8: 13–23

  • Smeyne RJ, Vendrell M, Hayward M, Baker SJ, Miao GG, Schilling K, Robertson LM, Curran T, Morgan JI . 1993 Nature 363: 166–169

  • Spence HJ, Johnston I, Ewart K, Buchanan SJ, Fitzgerald U, Ozanne BW . 2000 Oncogene 19: 1266–1276

  • Sunters A, McCluskey J, Grigoriadis AE . 1998 Dev. Genet. 22: 386–397

  • Szabowski A, Maas-Szabowski N, Andrecht S, Kolbus A, Schorpp-Kistner M, Fusenig NE, Angel P . 2000 Cell. 103: 745–755

  • Thepot D, Weitzman JB, Barra J, Segretain D, Stinnakre MG, Babinet C, Yaniv M . 2000 Development 127: 143–153

  • Thomas DP, Sunters A, Gentry A, Grigoriadis AE . 2000 J. Cell. Sci. 113: 439–450

  • Treinies I, Paterson HF, Hooper S, Wilson R, Marshall CJ . 1999 Mol. Cell. Biol. 19: 321–329

  • Vallone D, Battista S, Pierantoni GM, Fedele M, Casalino L, Santoro M, Viglietto G, Fusco A, Verde P . 1997 EMBO J. 16: 5310–5321

  • Wang ZQ, Grigoriadis AE, Möhle-Steinlein U, Wagner EF . 1991 EMBO J. 10: 2437–2450

  • Wang ZQ, Liang J, Schellander K, Wagner EF, Grigoriadis AE . 1995 Cancer Res. 55: 6244–6251

  • Wang ZQ, Ovitt C, Grigoriadis AE, Möhle-Steinlein U, Rüther U, Wagner EF . 1992 Nature 360: 741–745

  • Weitzman JB, Fiette L, Matsuo K, Yaniv M . 2000 Mol. Cell. 6: 1109–1119

  • Werb Z . 1997 Cell. 91: 439–442

  • Wisdom R, Johnson RS, Moore C . 1999 EMBO J. 18: 188–197

  • Wisdom R, Verma IM . 1993 Mol. Cell. Biol. 13: 7429–7438

  • Wisdom R, Yen J, Rashid D, Verma IM . 1992 Genes Dev. 6: 667–675

  • Yang DD, Kuan CY, Whitmarsh AJ, Rincon M, Zheng TS, Davis RJ, Rakic P, Flavell RA . 1997 Nature 389: 865–870

  • Yen J, Wisdom RM, Tratner I, Verma IM . 1991 Proc. Natl. Acad. Sci. USA 88: 5077–5081

  • Young MR, Li JJ, Rincon M, Flavell RA, Sathyanarayana BK, Hunziker R, Colburn N . 1999 Proc. Natl. Acad. Sci. USA 96: 9827–9832

Download references

Acknowledgements

The authors thank A Fleischmann, A Grigoriadis, K Matsuo, M Sibilia and M Schorpp-Kistner for critical comments on the manuscript. The authors acknowledge the financial support from the EC TMR network.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jochum, W., Passegué, E. & Wagner, E. AP-1 in mouse development and tumorigenesis. Oncogene 20, 2401–2412 (2001). https://doi.org/10.1038/sj.onc.1204389

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204389

Keywords

This article is cited by

Search

Quick links