Abstract
Fos and Jun family proteins regulate the expression of a myriad of genes in a variety of tissues and cell types. This functional versatility emerges from their interactions with related bZIP proteins and with structurally unrelated transcription factors. These interactions at composite regulatory elements produce nucleoprotein complexes with high sequence-specificity and regulatory selectivity. Several general principles including binding cooperativity and conformational adaptability have emerged from studies of regulatory complexes containing Fos-Jun family proteins. The structural properties of Fos-Jun family proteins including opposite orientations of heterodimer binding and the ability to bend DNA can contribute to the assembly and functions of such complexes. The cooperative recruitment of transcription factors, coactivators and chromatin remodeling factors to promoter and enhancer regions generates multiprotein transcription regulatory complexes with cell- and stimulus-specific transcriptional activities. The gene-specific architecture of these complexes can mediate the selective control of transcriptional activity.
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References
Agalioti T, Lomvardas S, Parekh B, Yie J, Maniatis T, Thanos D . 2000 Cell 103: 667â678
Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL . 1999 Cell 96: 143â152
Aho S, Buisson M, Pajunen T, Ryoo YW, Giot JF, Gruffat H, Sergeant A, Uitto J . 2000 J. Cell. Biol. 148: 1165â1176
Alam J, Wicks C, Stewart D, Gong P, Touchard C, Otterbein S, Choi AM, Burow ME, Tou J . 2000 J. Biol. Chem. 275: 27694â27702
Aronheim A, Zandi E, Hennemann H, Elledge SJ, Karin M . 1997 Mol. Cell. Biol. 17: 3094â3102
Bakin AV, Curran T . 1999 Science 283: 387â390
Bannister AJ, Kouzarides T . 1995 EMBO J. 14: 4758â4762
Baranger AM, Palmer CR, Hamm MK, Giebler HD, Brauweiler A, Nyborg JK and Schepartz A . 1995 Nature 376: 606â608
Bassuk AG, Leiden JM . 1995 Immunity 3: 223â237
Basuyaux JP, Ferreira E, Stehelin D, Buttice G . 1997 J. Biol. Chem. 272: 26188â26195
Benkhelifa S, Provot S, Lecoq O, Pouponnot C, Calothy G, Felder-Schmittbuhl MP . 1998 Oncogene 17: 247â254
Boehlk S, Fessele S, Mojaat A, Miyamoto NG, Werner T, Nelson EL, Schlondorff D, Nelson PJ . 2000 Eur. J. Immunol. 30: 1102â1112
Brodin G, Ahgren A, ten Dijke P, Heldin CH, Heuchel R . 2000 J. Biol. Chem. 275: 29023â29030
Buttice G, Duterque-Coquillaud M, Basuyaux JP, Carrere S, Kurkinen M, Stehelin D . 1996 Oncogene 13: 2297â2306
Caelles C, Gonzalez-Sancho JM, Munoz A . 1997 Genes Dev. 11: 3351â3364
Chen BK, Chang WC . 2000 Proc. Natl. Acad. Sci. USA 97: 10406â10411
Chen L, Glover JN, Hogan PG, Rao A, Harrison SC . 1998 Nature 392: 42â48
Chen L, Oakley MG, Glover JN, Jain J, Dervan PB, Hogan PG, Rao A, Verdine GL . 1995 Curr. Biol. 5: 882â889
Chen X, Rubock MJ, Whitman M . 1996 Nature 383: 691â696
Chytil M, Peterson BR, Erlanson DA, Verdine GL . 1998 Proc. Natl. Acad. Sci. USA 95: 14076â14081
Claret FX, Hibi M, Dhut S, Toda T, Karin M . 1996 Nature 383: 453â457
Curran T, Teich NM . 1982 J. Virol. 42: 114â122
Curran T, Franza BR . 1988 Cell 55: 395â397
De Cesare D, Palazzolo M, Berthelsen J, Blasi F . 1997 J. Biol. Chem. 272: 23921â23929
De Graeve F, Bahr A, Sabapathy KT, Hauss C, Wagner EF, Kedinger C, Chatton B . 1999 Oncogene 18: 3491â3500
Derynck R, Zhang Y, Feng XH . 1998 Cell 95: 737â740
Diamond MI, Miner JN, Yoshinaga SK, Yamamoto KR . 1990 Science 249: 1266â1272
Diebold RJ, Rajaram N, Leonard DA, Kerppola TK . 1998 Proc. Natl. Acad. Sci. USA 95: 7915â7920
Dlakic M, Grinberg AV, Leonard DA, Kerppola TK . 2001 EMBO J. 20: 1â14
D'Orazio D, Besser D, Marksitzer R, Kunz C, Hume DA, Kiefer B, Nagamine Y . 1997 Gene 201: 179â187
Du W, Thanos D, Maniatis T . 1993 Cell 74: 887â898
Duncliffe KN, Bert AG, Vadas MA, Cockerill PN . 1997 Immunity 6: 175â185
Echlin DR, Tae HJ, Mitin N, Taparowsky EJ . 2000 Oncogene 19: 1752â1763
Eckert RL, Crish JF, Banks EB, Welter JF . 1997 J. Invest. Dermatol. 109: 501â509
Ellenberger TE, Brandl CJ, Struhl K, Harrison SC . 1992 Cell 71: 1223â1237
Falvo JV, Brinkman BM, Tsytsykova AV, Tsai EY, Yao TP, Kung AL, Goldfeld AE . 2000a Proc. Natl. Acad. Sci. USA 97: 3925â3929
Falvo JV, Parekh BS, Lin CH, Fraenkel E, Maniatis T . 2000b Mol. Cell. Biol. 20: 4814â4825
Falvo JV, Uglialoro AM, Brinkman BM, Merika M, Parekh BS, Tsai EY, King HC, Morielli AD, Peralta EG, Maniatis T, Thanos D, Goldfeld AE . 2000c Mol. Cell. Biol. 20: 2239â2247
Fu SL, Waha A, Vogt PK . 2000 Oncogene 19: 3537â3545
Fujii Y, Shimizu T, Toda T, Yanagida M, Hakoshima T . 2000 Nat. Struct. Biol. 7: 889â893
Giese K, Kingsley C, Kirshner JR, Grosschedl R . 1995 Genes Dev. 9: 995â1008
Glover JN, Harrison SC . 1995 Nature 373: 257â261
Gottschalk LR, Giannola DM, Emerson SG . 1993 J. Exp. Med. 178: 1681â1692
Graves BJ, Petersen JM . 1998 Adv. Cancer Res. 75: 1â55
Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA, Wagner EF . 1994 Science 266: 443â448
Gum R, Lengyel E, Juarez J, Chen JH, Sato H, Seiki M, Boyd D . 1996 J. Biol. Chem. 271: 10672â10680
Gutman A, Wasylyk B . 1990 EMBO J. 9: 2241â2246
Hai T, Curran T . 1991 Proc. Natl. Acad. Sci. USA 88: 3720â3724
Hernandez-Munain C, Roberts JL, Krangel MS . 1998 Mol. Cell. Biol. 18: 3223â3233
Hilberg F, Aguzzi A, Howells N, Wagner EF . 1993 Nature 365: 179â181
Hoey T, Sun YL, Williamson K, Xu X . 1995 Immunity 2: 461â472
Hsu W, Kerppola TK, Chen PL, Curran T, Chen-Kiang S . 1994 Mol. Cell. Biol. 14: 268â276
Hua X, Liu X, Ansari DO, Lodish HF . 1998 Genes Dev. 12: 3084â3095
Iacobelli M, Wachsman W, McGuire KL . 2000 J. Immunol. 165: 860â868
Jain J, McCaffrey PG, Miner Z, Kerppola TK, Lambert JN, Verdine GL, Curran T, Rao A . 1993a Nature 365: 352â355
Jain J, Miner Z, Rao A . 1993b J. Immunol. 151: 837â848
Jaiswal AK . 2000 Free Radic. Biol. Med. 29: 254â262
Jang SI, Karaman-Jurukovska N, Morasso MI, Steinert PM, Markova NG . 2000 J. Biol. Chem. 275: 15295â15304
Johnson RS, Spiegelman BM, Papaioannou V . 1992 Cell 71: 577â586
Johnson RS, van Lingen B, Papaioannou VE, Spiegelman BM . 1993 Genes Dev. 7: 1309â1317
Jones JB, Kern SE . 2000 Nucleic Acids Res. 28: 2363â2368
Jonk LJ, Itoh S, Heldin CH, ten Dijke P, Kruijer W . 1998 J. Biol. Chem. 273: 21145â21152
Kataoka K, Fujiwara KT, Noda M, Nishizawa M . 1994a Mol. Cell. Biol. 14: 7581â7591
Kataoka K, Igarashi K, Itoh K, Fujiwara KT, Noda M, Yamamoto M, Nishizawa M . 1995 Mol. Cell. Biol. 15: 2180â2190
Kataoka K, Noda M, Nishizawa M . 1994b Mol. Cell. Biol. 14: 700â712
Kataoka K, Noda M, Nishizawa M . 1996 Oncogene 12: 53â62
Kawana M, Lee ME, Quertermous EE, Quertermous T . 1995 Mol. Cell. Biol. 15: 4225â4231
Kerppola TK . 1998 Structure 6: 549â554
Kerppola TK, Curran T . 1991 Cell 66: 317â326
Kerppola TK, Curran T . 1993 Mol. Cell. Biol. 13: 5479â5489
Kerppola TK, Curran T . 1994a Oncogene 9: 3149â3158
Kerppola TK, Curran T . 1994b Oncogene 9: 675â684
Kerppola TK, Luk D, Curran T . 1993 Mol. Cell. Biol. 13: 3782â3791
Kirstein M, Sanz L, Quinones S, Moscat J, Diaz-Meco MT, Saus J . 1996 J. Biol. Chem. 271: 18231â18236
Kodandapani R, Pio F, Ni CZ, Piccialli G, Klemsz M, McKercher S, Maki RA, Ely KR . 1996 Nature 380: 456â460
Konig H, Ponta H, Rahmsdorf HJ, Herrlich P . 1992 EMBO J. 11: 2241â2246
Kovary K, Bravo R . 1991 Mol. Cell. Biol. 11: 2451â2459
Kovary K, Bravo R . 1992 Mol. Cell. Biol. 12: 5015â5023
Kramer B, Wiegmann K, Kronke M . 1995 J. Biol. Chem. 270: 6577â6583
Lallemand D, Spyrou G, Yaniv M, Pfarr CM . 1997 Oncogene 14: 819â830
Landschulz WH, Johnson PF, McKnight SL . 1988 Science 240: 1759â1764
Lee SK, Kim HJ, Na SY, Kim TS, Choi HS, Im SY, Lee JW . 1998 J. Biol. Chem. 273: 16651â16654
Lee SK, Kim JH, Lee YC, Cheong J, Lee JW . 2000a J. Biol. Chem. 275: 12470â12474
Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW . 2000b Mol. Endocrinol. 14: 915â925
Lefstin JA, Yamamoto KR . 1998 Nature 392: 885â888
Leonard DA, Kerppola TK . 1998 Nat. Struct. Biol. 5: 877â881
Leonard DA, Rajaram N, Kerppola TK . 1997 Proc. Natl. Sci. USA 13: 4913â4918
Li B, Tournier C, Davis RJ, Flavell RA . 1999 EMBO J 18: 420â432
Li L, Chambard JC, Karin M, Olson EN . 1992 Genes Dev. 6: 676â689
Liberati NT, Datto MB, Frederick JP, Shen X, Wong C, Rougier-Chapman EM, Wang XF . 1999 Proc. Natl. Acad. Sci. USA 96: 4844â4849
Logan SK, Garabedian MJ, Campbell CE, Werb Z . 1996 J. Biol. Chem. 271: 774â782
Maki Y, Bos TJ, Davis C, Starbuck M, Vogt PK . 1987 Proc. Natl. Acad. Sci. USA 84: 2848â2852
Martin ME, Piette J, Yaniv M, Tang WJ, Folk WR . 1988 Proc. Natl. Acad. Sci. USA 85: 5839â5843
Mayall TP, Sheridan PL, Montminy MR, Jones KA . 1997 Genes Dev. 11: 887â899
McBride K, Nemer M . 1998 Mol. Cell. Biol. 18: 5073â5081
McCabe LR, Kockz M, Lian J, Stein G . 1995 Exp. Cell Res. 218: 255â262
McCabe LR, Banerjee C, Kundu R, Harrison RJ, Dobner PR, Stein JL, Lian JB, Stein GS . 1996 Endocrinology 137: 4398â4408
McCaffrey PG, Luo C, Kerppola TK, Jain J, Badalian TM, Ho AM, Burgeon E, Lane WS, Lambert JN, Curran T, Verdine GV, Rao A, Hogan PG . 1993 Science 262: 750â754
Merika M, Williams AJ, Chen G, Collins T, Thanos D . 1998 Mol. Cell. 1: 277â287
Metz R, Bannister AJ, Sutherland JA, Hagemeier C, O'Rourke EC, Cook A, Bravo R, Kouzarides T . 1994 Mol. Cell. Biol. 14: 6021â6029
Min W, Ghosh S, Lengyel P . 1996 Mol. Cell. Biol. 16: 359â368
Moinova HR, Mulcahy RT . 1999 Biochem. Biophys. Res. Commun. 261: 661â668
Monteclaro FS, Vogt PK . 1993 Proc. Natl. Acad. Sci. USA 90: 6726â6730
Moreau A, Yotov WV, Glorieux FH, St-Arnaud R . 1998 Mol. Cell. Biol. 18: 1312â1321
Moulton KS, Semple K, Wu H, Glass CK . 1994 Mol. Cell. Biol. 14: 4408â4418
Nakabeppu Y, Ryder K, Nathans D . 1988 Cell 55: 907â915
Nead MA, Baglia LA, Antinore MJ, Ludlow JW, McCance DJ . 1998 EMBO J. 17: 2342â2352
Nerlov C, De Cesare D, Pergola F, Caracciolo A, Blasi F, Johnsen M, Verde P . 1992 EMBO J. 11: 4573â4582
Nguyen T, Huang HC, Pickett CB . 2000 J. Biol. Chem. 275: 15466â15473
Noti JD, Reinemann C, Petrus MN . 1996 Mol. Immunol. 33: 115â127
Palazzolo M, Berthelsen J, De Cesare D, Blasi F . 2000 Eur. J. Biochem. 267: 5427â5437
Perini G, Oetjen E, Green MR . 1999 J. Biol. Chem. 274: 13970â13977
Perkins D, Wang Z, Donovan C, He H, Mark D, Guan G, Wang Y, Walunas T, Bluestone J, Listman J . 1996 J. Immunol. 156: 4154â4159
Peterson BR, Sun LJ, Verdine GL . 1996 Proc. Natl. Acad. Sci. USA 93: 13671â13676
Pognonec P, Boulukos KE, Aperlo C, Fujimoto M, Ariga H, Nomoto A, Kato H . 1997 Oncogene 14: 2091â2098
Qian Z, Brunovskis P, Lee L, Vogt PK, Kung HJ . 1996 J. Virol. 70: 7161â7170
Qing J, Zhang Y, Derynck R . 2000 J. Biol. Chem. 275: 38802â38812
Rajaram N, Kerppola TK . 1997 EMBO J. 16: 2917â2925
Ramirez-Carrozzi VR, Kerppola TK . 2001a Proc. Natl. Acad. Sci. USA 98: 4893â4898
Ramirez-Carrozzi VR, Kerppola TK . 2001b J. Mol. Biol. 305: 411â427
Rao A, Luo C, Hogan PG . 1997 Annu. Rev. Immunol. 15: 707â747
Rauscher FJD, Voulalas PJ, Franza Jr BR, Curran T . 1988 Genes Dev. 2: 1687â1699
Robertson LM, Kerppola TK, Vendrell M, Luk D, Smeyne RJ, Bocchiaro C, Morgan JI, Curran T . 1995 Neuron 14: 241â252
Rooney JW, Hoey T, Glimcher LH . 1995 Immunity 2: 473â483
Rushmore TH, Pickett CB . 1990 J. Biol. Chem. 265: 14648â14653
Sano Y, Harada J, Tashiro S, Gotoh-Mandeville R, Maekawa T, Ishii S . 1999 J. Biol. Chem. 274: 8949â8957
Sato M, Morii E, Takebayashi-Suzuki K, Yasui N, Ochi T, Kitamura Y, Nomura S . 1999 Biochem. Biophys. Res. Commun. 254: 384â387
Schorpp-Kistner M, Wang ZQ, Angel P, Wagner EF . 1999 EMBO J 18: 934â948
Schreiber M, Wang Z, Jochum W, Fetka I, Elliott C, Wagner EF . 2000 Development 127: 4937â4948
Schule R, Umesono K, Mangelsdorf DJ, Bolado J, Pike JW, Evans RM . 1990 Cell 61: 497â504
Schumacher MA, Goodman RH, Brennan RG . 2000 J. Biol. Chem. 275: 35242â35247
Shaw JP, Utz PJ, Durand DB, Toole JJ, Emmel EA, Crabtree GR . 1988 Science 241: 202â205
Shi Y, Wang YF, Jayaraman L, Yang H, Massague J, Pavletich NP . 1998 Cell 94: 585â594
Sieweke MH, Tekotte H, Frampton J, Graf T . 1996 Cell 85: 49â60
Sonnenberg JL, Macgregor-Leon PF, Curran T, Morgan JI . 1989 Neuron 3: 359â365
Spicuglia S, Payet D, Tripathi RK, Rameil P, Verthuy C, Imbert J, Ferrier P, Hempel WM . 2000 EMBO J. 19: 2034â2045
Stein B, Baldwin AS, Ballard DW, Greene WC, Angel P, Herrlich P . 1993 EMBO J. 12: 3897â3891
Stranick KS, Zambas DN, Uss AS, Egan RW, Billah MM, Umland SP . 1997 J. Biol. Chem. 272: 16453â16465
Tan S, Richmond TJ . 1998 Nature 391: 660â666
Thanos D, Maniatis T . 1995 Cell 83: 1091â1100
Thepot D, Weitzman JB, Barra J, Segretain D, Stinnakre MG, Babinet C, Yaniv M . 2000 Development 127: 143â153
Tsai EY, Jain J, Pesavento PA, Rao A, Goldfeld AE . 1996a Mol. Cell. Biol. 16: 459â467
Tsai EY, Yie J, Thanos D, Goldfeld AE . 1996b Mol. Cell. Biol. 16: 5232â5244
Tsai EY, Falvo JV, Tsytsykova AV, Barczak AK, Reimold AM, Glimcher LH, Fenton MJ, Gordon DC, Dunn IF, Goldfeld AE . 2000 Mol. Cell. Biol. 20: 6084â6094
Ubeda M, Vallejo M, Habener JF . 1999 Mol. Cell. Biol. 19: 7589â7599
Ullman KS, Northrop JP, Admon A, Crabtree GR . 1993 Genes. Dev. 7: 188â196
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: 479â487
van Dam H, Huguier S, Kooistra K, Baguet J, Vial E, van der Eb AJ, Herrlich P, Angel P, Castellazzi M . 1998 Genes. Dev. 12: 1227â1239
Venugopal R, Jaiswal AK . 1998 Oncogene 17: 3145â3156
Virbasius CM, Wagner S, Green MR . 1999 Mol. Cell. 4: 219â228
Wang CY, Bassuk AG, Boise LH, Thompson CB, Bravo R, Leiden JM . 1994 Mol. Cell. Biol. 14: 1153â1159
Wang ZQ, Ovitt C, Grigoriadis AE, Mohle-Steinlein U, Ruther U, Wagner EF . 1992 Nature 360: 741â745
Wolfe SA, Zhou P, Dotsch V, Chen L, You A, Ho SN, Crabtree GR, Wagner G, Verdine GL . 1997 Nature 385: 172â176
Wong C, Rougier-Chapman EM, Frederick JP, Datto MB, Liberati NT, Li JM, Wang XF . 1999 Mol. Cell. Biol. 19: 1821â1830
Wu H, Moulton K, Horvai A, Parik S, Glass CK . 1994 Mol. Cell. Biol. 14: 2129â2139
Yie J, Merika M, Munshi N, Chen G, Thanos D . 1999 EMBO J. 18: 3074â3089
Zhang X, Wrzeszczynska MH, Horvath CM, Darnell Jr JE . 1999 Mol. Cell. Biol. 19: 7138â7146
Zhang Y, Derynck R . 2000 J. Biol. Chem. 275: 16979â16985
Zhang Y, Feng XH, Derynck R . 1998 Nature 394: 909â913
Zhou P, Sun LJ, Dotsch V, Wagner G, Verdine GL . 1998 Cell 92: 687â696
Acknowledgements
We apologize to the many people whose work could not be cited due to space limitations. We thank Mensur Dlakic, Asya Grinberg and Nirmala Rajaram for helpful discussions during preparation of the manuscript and Ann E Goldfeld (Harvard Medical School), Andy Sharroks (Manchester University), Laura McCabe (Michigan State University), Helen Moinova (Case Western Reserve University), Moshe Yaniv (Institute Pasteur) and Thomas Herdegen (University of Kiel) for comments.
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Chinenov, Y., Kerppola, T. Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity. Oncogene 20, 2438â2452 (2001). https://doi.org/10.1038/sj.onc.1204385
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