Abstract
The c-fos enhancer can be activated by many signaling pathways through distinct elements of the enhancer. The enhancer contains at its core the serum response element (SRE) that binds serum response factor (SRF). On the 5′ side of the SRE is a site for p62TCF which binds only when SRF is bound as well. p62TCF is encoded by three ets-related genes, Elk-1, SAP1 and SAP2. Each of these factors contain a transcriptional activation domain that is activated by phosphorylation by MAP kinases. On the 3′ side of the SRE is the ‘c-fos AP1 site’ (FAP1) whose role has been less clear. We find here that the FAP1 site contributes strongly to phorbol ester (TPA) and Erk MAP kinase activation of the c-fos enhancer and that both the p62TCF and FAP1 sites are required for effective activation of the enhancer. We further find that the FAP1 site binds ATF1 and CREB from HeLa nuclear extracts and that the phosphorylation of these factors is induced by TPA. ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinases. These results suggest a signaling pathway in which Erk MAP kinase activates the c-fos enhancer by direct phosphorylation of p62TCF and by activation of Rsk related kinases that phosphorylate ATF1 and CREB.
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References
Attar RM and Gilman MZ . 1992 Mol Cell Biol 12: 2432–2443
Berkowitz LA, Riabowol KT and Gilman MZ . 1989 Mol Cell Biol 9: 4272–4281
Bruder JT, Heidecker G and Rapp UR . 1992 Genes Dev 6: 545–556
Chen X and Prywes R . 1999 Mol Cell Biol 19: 4695–4702
Clarke N, Arenzana N, Hai T, Minden A and Prywes R . 1998 Mol Cell Biol 18: 1065–1073
De Cesare D, Fimia GM and Sassone-Corsi P . 1999 Trends Biochem Sci 24: 281–285
De Cesare D, Jacquot S, Hanauer A and Sassone-Corsi P . 1998 Proc Natl Acad Sci USA 95: 12202–12207
Deak M, Clifton AD, Lucocq LM and Alessi DR . 1998 EMBO J 17: 4426–4441
Fisch TM, Prywes R and Roeder RG . 1987 Mol Cell Biol 7: 3490–3502
Fisch TM, Prywes R, Simon MC and Roeder RG . 1989 Genes Dev 3: 198–211
Fu XY and Zhang JJ . 1993 Cell 74: 1135–1145
Gille H, Sharrocks AD and Shaw PE . 1992 Nature 358: 414–417
Ginty DD, Bonni A and Greenberg ME . 1994 Cell 77: 713–725
Gonzalez GA and Montminy MR . 1989 Cell 59: 675–680
Graham R and Gilman M . 1991 Science 251: 189–192
Grueneberg DA, Henry RW, Brauer A, Novina CD, Cheriyath V, Roy AL and Gilman M . 1997 Genes Dev 11: 2482–2493
Gualberto A, LePage D, Pons G, Mader SL, Park K, Atchison ML and Walsh K . 1992 Mol Cell Biol 12: 4209–4214
Hill CS, Wynne J and Treisman R . 1995 Cell 81: 1159–1170
Iordanov M, Bender K, Ade T, Schmid W, Sachsenmaier C, Engel K, Gaestel M, Rahmsdorf HJ and Herrlich P . 1997 EMBO J 16: 1009–1022
Johansen FE and Prywes R . 1995 Biochim Biophys Acta 1242: 1–10
Kim DW, Cheriyath V, Roy AL and Cochran BH . 1998 Mol Cell Biol 18: 3310–3320
Liu F, Thompson MA, Wagner S, Greenberg ME and Green MR . 1993 J Biol Chem 268: 6714–6720
Marais R, Wynne J and Treisman R . 1993 Cell 73: 381–393
Matthews RP, Guthrie CR, Wailes LM, Zhao X, Means AR and McKnight GS . 1994 Mol Cell Biol 14: 6107–6116
Metz R and Ziff E . 1991 Oncogene 6: 2165–2178
Miranti CK, Ginty DD, Huang G, Chatila T and Greenberg ME . 1995 Mol Cell Biol 15: 3672–3684
Mitchell PJ and Tjian R . 1989 Science 245: 371–378
Montminy M . 1997 Annu Rev Biochem 66: 807–822
Pierrat B, Correia JS, Mary JL, Tomas-Zuber M and Lesslauer W . 1998 J Biol Chem 273: 29661–29671
Prywes R and Roeder RG . 1986 Cell 47: 777–784
Qiu RG, Chen J, McCormick F and Symons M . 1995 Proc Natl Acad Sci USA 92: 11781–11785
Rehfuss RP, Walton KM, Loriaux MM and Goodman RH . 1991 J Biol Chem 266: 18431–18434
Robertson LM, Kerppola TK, Vendrell M, Luk D, Smeyne RJ, Bocchiaro C, Morgan JI and Curran T . 1995 Neuron 14: 241–252
Sadowski HB, Shuai K, Darnell Jr JE and Gilman MZ . 1993 Science 261: 1739–1744
Sambrook J, Fritsch E and Maniatis T . 1989 Molecular cloning a laboratory manual Second edn Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Sassone-Corsi P, Visvader J, Ferland L, Mellon PL and Verma IM . 1988 Genes Dev 2: 1529–1538
Shaw PE, Schroter H and Nordheim A . 1989 Cell 56: 563–572
Sheng M, McFadden G and Greenberg ME . 1990 Neuron 4: 571–582
Siegfried Z and Ziff EB . 1989 Oncogene 4: 3–11
Sotiropoulos A, Gineitis D, Copeland J and Treisman R . 1999 Cell 98: 159–169
Tan Y, Rouse J, Zhang A, Cariati S, Cohen P and Comb MJ . 1996 EMBO J 15: 4629–4642
Treisman R . 1992 Trends Biochem Sci 17: 423–426
Treisman R . 1994 Curr Opin Genet Dev 4: 96–101
Treisman R . 1996 Curr Opin Cell Biol 8: 205–215
Trivier E, De Cesare D, Jacquot S, Pannetier S, Zackai E, Young I, Mandel JL, Sassone-Corsi P and Hanauer A . 1996 Nature 384: 567–570
Wagner BJ, Hayes TE, Hoban CJ and Cochran BH . 1990 EMBO J 9: 4477–4484
Wang Y, Falasca M, Schlessinger J, Malstrom S, Tsichlis P, Settleman J, Hu W, Lim B and Prywes R . 1998 Cell Growth Differ 9: 513–522
Whitmarsh AJ, Shore P, Sharrocks AD and Davis RJ . 1995 Science 269: 403–407
Whitmarsh AJ, Yang SH, Su MS, Sharrocks AD and Davis RJ . 1997 Mol Cell Biol 17: 2360–2371
Xing J, Ginty DD and Greenberg ME . 1996 Science 273: 959–963
Xing J, Kornhauser JM, Xia Z, Thiele EA and Greenberg ME . 1998 Mol Cell Biol 18: 1946–1955
Young ID . 1988 J Med Genet 25: 344–348
Zhu C, Johansen FE and Prywes R . 1997 Mol Cell Biol 17: 4957–4966
Acknowledgements
We thank Dr Michael Greenberg for RSK and CREB plasmids and anti-CREB sera and Dr Tsonwin Hai for anti-ATF family sera. This work was supported by grant CA 50329 from the National Cancer Institute and the National Institutes of Health to R Prywes.
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Wang, Y., Prywes, R. Activation of the c-fos enhancer by the Erk MAP kinase pathway through two sequence elements: the c-fos AP-1 and p62TCF sites. Oncogene 19, 1379–1385 (2000). https://doi.org/10.1038/sj.onc.1203443
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DOI: https://doi.org/10.1038/sj.onc.1203443
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