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 cell proliferation and survival

Abstract

A plethora of physiological and pathological stimuli induce and activate a group of DNA binding proteins that form AP-1 dimers. These proteins include the Jun, Fos and ATF subgroups of transcription factors. Recent studies using cells and mice deficient in individual AP-1 proteins have begun to shed light on their physiological functions in the control of cell proliferation, neoplastic transformation and apoptosis. Above all such studies have identified some of the target genes that mediate the effects of AP-1 proteins on cell proliferation and death. There is evidence that AP-1 proteins, mostly those that belong to the Jun group, control cell life and death through their ability to regulate the expression and function of cell cycle regulators such as Cyclin D1, p53, p21cip1/waf1, p19ARF and p16. Amongst the Jun proteins, c-Jun is unique in its ability to positively regulate cell proliferation through the repression of tumor suppressor gene expression and function, and induction of cyclin D1 transcription. These actions are antagonized by JunB, which upregulates tumor suppressor genes and represses cyclin D1. An especially important target for AP-1 effects on cell life and death is the tumor suppressor p53, whose expression as well as transcriptional activity, are modulated by AP-1 proteins.

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

Similar content being viewed by others

References

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

  • Albanese C, Johnson J, Watanabe G, Eklund N, Vu D, Arnold A, Pestell RG . 1995 J. Biol. Chem. 270: 23589–23597

  • Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M . 1987 Cell 49: 729–739

  • Angel P, Allegretto EA, Okino ST, Hattori K, Boyle WJ, Hunter T, Karin M . 1988a Nature 332: 166–171

  • Angel P, Hattori K, Smeal T, Karin M . 1988b Cell 55: 875–885

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

  • Aronheim A, Zandi E, Hennemann H, Elledge SJ, Karin M . 1997 Mol. Cell. Biol. 17: 3094–3102

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

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

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

  • Beier F, Lee RJ, Taylor AC, Pestell RG, LuValle P . 1999 Proc. Natl. Acad. Sci. USA 96: 1433–1438

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

  • Bissonnette N, Hunting DJ . 1998 Oncogene 16: 3461–3469

  • Bohmann D, Bos TJ, Admon A, Nishimura T, Vogt PK, Tjian R . 1987 Science 238: 1386–1392

  • Bos TJ, Monteclaro FS, Mitsunobu F, Ball Jr AR, Chang CH, Nishimura T, Vogt PK . 1990 Genes. Dev. 4: 1677–1687

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

  • Brenner DA, O'Hara M, Angel P, Chojkier M, Karin M . 1989 Nature 337: 661–663

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

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

  • Chen YR, Wang X, Templeton D, Davis RJ, Tan TH . 1996 J. Biol. Chem. 271: 31929–31936

  • Chiu R, Boyle WJ, Meek J, Smeal T, Hunter T, Karin M . 1988 Cell 54: 541–552

  • Chiu R, Angel P, Karin M . 1989 Cell 59: 979–986

  • Deng T, Karin M . 1993 Genes. Dev. 7: 479–490

  • Devary Y, Gottlieb RA, Lau LF, Karin M . 1991 Mol. Cell. Biol. 11: 2804–2811

  • Devary Y, Gottlieb RA, Smeal T, Karin M . 1992 Cell 71: 1081–1091

  • 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 Cell. Biol. 127: 1717–1727

  • Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ, Hancock DC . 1992 Cell 69: 119–128

  • Freeman RS, Estus S, Johnson Jr. EM . 1994 Neuron 12: 343–355

  • Fuchs SY, Adler V, Buschmann T, Yin Z, Wu X, Jones SN, Ronai Z . 1998 Genes. Dev. 12: 2658–2663

  • Fujiwara KT, Kataoka K, Nishizawa M . 1993 Oncogene 8: 2371–2380

  • Goldgaber D, Harris HW, Hla T, Maciag T, Donnelly RJ, Jacobsen JS, Vitek MP, Gajdusek DC . 1989 Proc. Natl. Acad. Sci. USA 86: 7606–7610

  • Gupta S, Campbell D, Derijard B, Davis RJ . 1995 Science 267: 389–393

  • Halazonetis TD, Georgopoulos K, Greenberg ME, Leder P . 1988 Cell 55: 917–924

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

  • Han TH, Prywes R . 1995 Mol. Cell. Biol. 15: 2907–2915

  • Han J, Jiang Y, Li Z, Kravchenko VV, Ulevitch RJ . 1997 Nature 386: 296–299

  • Havarstein LS, Morgan IM, Wong WY, Vogt PK . 1992 Proc. Natl. Acad. Sci. USA 89: 618–622

  • Herber B, Truss M, Beato M, Muller R . 1994 Oncogene 9: 1295–1304

  • Herdegen T, Claret FX, Kallunki T, Martin-Villalba A, Winter C, Hunter T, Karin M . 1998 J. Neurosci. 18: 5124–5135

  • Herr I, van Dam H, Angel P . 1994 Carcinogenesis 15: 1105–1113

  • Herrlich P, Blattner C, Knebel A, Bender K, Rahmsdorf HJ . 1997 Biol. Chem. 378: 1217–1229

  • Herrlich P, Ponta H, Rahmsdorf HJ . 1992 Rev. Physiol. Biochem. Pharmacol. 119: 187–223

  • Hibi M, Lin A, Smeal T, Minden A, Karin M . 1993 Genes. Dev. 7: 2135–2148

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

  • Hill CS, Wynne J, Treisman R . 1994 EMBO J. 13: 5421–5432

  • Holbrook NJ, Fornace Jr AJ . 1991 New Biol. 3: 825–833

  • Holt JT, Gopal TV, Moulton AD, Nienhuis AW . 1986 Proc. Natl. Acad. Sci. USA 83: 4794–4798

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

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

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

  • Kallunki T, Deng T, Hibi M, Karin M . 1996 Cell 87: 929–939

  • Karin M . 1995 J. Biol. Chem. 270: 16483–16486

  • Karin M . 1998 Ann. NY Acad. Sci. 851: 139–146

  • Karin M, Liu Z, Zandi E . 1997 Curr. Opin. Cell. Biol. 9: 240–246

  • Kasibhatla S, Brunner T, Genestier L, Echeverri F, Mahboubi A, Green DR . 1998 Molecular. Cell. 1: 543–551

  • Kataoka K, Noda M, Nishizawa M . 1994 Mol. Cell. Biol. 14: 700–712

  • Kataoka K, Igarashi K, Itoh K, Fujiwara KT, Noda M, Yamamoto M, Nishizawa M . 1995 Mol. Cell. Biol. 15: 2180–2190

  • Kenney AM, Kocsis JD . 1998 J. Neurosci. 18: 1318–1328

  • Kim SJ, Angel P, Lafyatis R, Hattori K, Kim KY, Sporn MB, Karin M, Roberts AB . 1990 Mol. Cell. Biol. 10: 1492–1497

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

  • Kouzarides T, Ziff E . 1988 Nature 336: 646–651

  • Kovary K, Bravo R . 1991 Mol. Cell. Biol. 11: 4466–4472

  • Kranenburg O, vander Eb AJ, Zantema A . 1996 EMBO J. 15: 46–54

  • Kuan CY, Yang DD, Samanta Roy DR, Davis RJ, Rakic P, Flavell RA . 1999 Neuron 22: 667–676

  • Laiho M, Ronnstrand L, Heino J, Decaprio JA, Ludlow JW, Livingston DM, Massague J . 1991 Mol. Cell. Biol. 11: 972–978

  • Lamph WW, Wamsley P, Sassone-Corsi P, Verma IM . 1988 Nature 334: 629–631

  • Lane DP . 1992 Nature 358: 15–16

  • Lee W, Haslinger A, Karin M, Tjian R . 1987a Nature 325: 368–372

  • Lee W, Mitchell P, Tjian R . 1987b Cell 49: 741–752

  • Le-Niculescu H, Bonfoco E, Kasuya Y, Claret FX, Green DR, Karin M . 1999 Mol. Cell. Biol. 19: 751–763

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

  • Liu ZG, Hsu H, Goeddel DV, Karin M . 1996 Cell 87: 565–576

  • Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T . 1993 Nature 362: 847–849

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

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

  • Muegge K, Williams TM, Kant J, Karin M, Chiu R, Schmidt A, Siebenlist U, Young HA, Durum SK . 1989 Science 246: 249–251

  • Natoli G, Costanzo A, Ianni A, Templeton DJ, Woodgett JR, Balsano C, Levrero M . 1997 Science 275: 200–203

  • Newton K, Strasser A . 2000 J. Exp. Med. 191: 195–200

  • Nishikura K, Murray JM . 1987 Mol. Cell. Biol. 7: 639–649

  • Nishina H, Fischer KD, Radvanyi L, Shahinian A, Hakem R, Rubie EA, Bernstein A, Mak TW, Woodgett JR, Penninger JM . 1997 Nature 385: 350–353

  • Nishizawa M, Kataoka K, Goto N, Fujiwara KT, Kawai S . 1989 Proc. Natl. Acad. Sci. USA 86: 7711–7715

  • Palmero I, Pantoja C, Serrano M . 1998 Nature 395: 125–126

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

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

  • 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

  • Qin XQ, Livingston DM, Kaelin Jr WG, Adams PD . 1994 Proc. Natl. Acad. Sci. USA 91: 10918–10922

  • Quantin B, Breathnach R . 1988 Nature 334: 538–539

  • Quelle DE, Zindy F, Ashmun RA, Sherr CJ . 1995 Cell 83: 993–1000

  • Rauscher FJD, Cohen DR, Curran T, Bos TJ, Vogt PK, Bohmann D, Tjian R, Franza Jr BR . 1988 Science 240: 1010–1016

  • Riabowol KT, Vosatka RJ, Ziff EB, Lamb NJ, Feramisco JR . 1988 Mol. Cell. Biol. 8: 1670–1676

  • Rüther U, Garber C, Komitowski D, Muller R, Wagner EF . 1987 Nature 325: 412–416

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

  • Ryder K, Nathans D . 1988 Proc. Natl. Acad. Sci. USA 85: 8464–8467

  • Ryseck RP, Bravo R . 1991 Oncogene 6: 533–542

  • Sabapathy K, Jochum W, Hochedlinger K, Chang L, Karin M, Wagner EF . 1999 Mech. Dev. 89: 115–124

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

  • 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, Mohle-Steinlein U, Tian J, Karin M, Angel P, Wagner EF . 1999 Genes Dev. 13: 607–619

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

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

  • Serfling E, Barthelmas R, Pfeuffer I, Schenk B, Zarius S, Swoboda R, Mercurio F, Karin M . 1989 EMBO J. 8: 465–473

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

  • Sheikh MS, Chen YQ, Smith ML, Fornace Jr AJ . 1997 Oncogene 14: 1875–1882

  • Sherr CJ . 1996 Science 274: 1672–1677

  • Sherr CJ . 1998 Genes Dev. 12: 2984–2991

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

  • Smith MJ, Prochownik EV . 1992 Blood 79: 2107–2115

  • Swaroop A, Xu JZ, Pawar H, Jackson A, Skolnick C, Agarwal N . 1992 Proc. Natl. Acad. Sci. USA 89: 266–270

  • 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

  • Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, Bar-Sagi D, Jones SN, Flavell RA, Davis RJ . 2000 Science 288: 870–874

  • van Dam H, Duyndam M, Rottier R, Bosch A, de Vries-Smits L, Herrlich P, Zantema A, Angel P, van der Eb AJ . 1993 EMBO J. 12: 479–487

  • van Straaten F, Muller R, Curran T, VanBeveren C, Verma IM . 1983 Proc. Natl. Acad. Sci. USA 80: 3183–3187

  • Vandel L, Montreau N, Vial E, Pfarr CM, Binetruy B, Castellazzi M . 1996 Mol. Cell. Biol. 16: 1881–1888

  • Verheij M, Bose R, Lin XH, Yao B, Jarvis WD, Grant S, Birrer MJ, Szabo E, Zon LI, Kyriakis JM, Haimovitz-Friedman A, Fuks Z, Kolesnick RN . 1996 Nature 380: 75–79

  • Vogelstein B, Lane D, Levine AJ . 2000 Nature 408: 307–310

  • Vousden KH . 2000 Cell 103: 691–694

  • Waldman T, Lengauer C, Kinzler KW, Vogelstein B . 1996 Nature 381: 713–716

  • Watson A, Eilers A, Lallemand D, Kyriakis J, Rubin LL, Ham J . 1998 J. Neurosci. 18: 751–762

  • Weber JD, Jeffers JR, Rehg JE, Randle DH, Lozano G, Roussel MF, Sherr CJ, Zambetti GP . 2000 Genes Dev. 14: 2358–2365

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

  • Wisdom R . 1999 Exp. Cell. Res. 253: 180–185

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

  • Wu BY, Fodor EJ, Edwards RH, Rutter WJ . 1989 J. Biol. Chem. 264: 9000–9003

  • Wu X, Levine AJ . 1994 Proc. Natl. Acad. Sci. USA 91: 3602–3606

  • Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME . 1995 Science 270: 1326–1331

  • Xu X, Raber J, Yang D, Su B, Mucke L . 1997 Proc. Natl. Acad. Sci. USA 94: 12655–12660

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

  • Yeh WC, Pompa JL, McCurrach ME, Shu HB, Elia AJ, Shahinian A, Ng M, Wakeham A, Khoo W, Mitchell K, El-Deiry WS, Lowe SW, Goeddel DV, Mak TW . 1998 Science 279: 1954–1958

  • Yoshida T, Shindo Y, Ohta K, Iba H . 1989 Oncogene Res. 5: 79–89

  • 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

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shaulian, E., Karin, M. AP-1 in cell proliferation and survival. Oncogene 20, 2390–2400 (2001). https://doi.org/10.1038/sj.onc.1204383

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204383

Keywords

This article is cited by

Search

Quick links