The Role and Regulation of the Jun Proteins in Response to Phorbol Ester and UV Light

  • Peter Angel
Part of the Progress in Gene Expression book series (PRGE)


The genetic program of all biological systems including the cells of mammals is extensively determined by the conditions of the immediate environment. Mammalian cells are exposed to many environmental cues such as cytokines or growth factors, as well as extraorganismic influences, such as heat, high concentrations of heavy metal ions, chemical carcinogens such as alkylating agents, tumor promoters, and radiation. A major adverse effect of the latter harmful substances is damage to DNA. By analogy to the bacterial system where exposure to DNA-damaging agents induces the SOS response (Little and Mount, 1982; Walker, 1985), mammalian cells actively respond to those agents by activating DNA repair enzymes and initiating a transcriptional induction response known as the UV response (Karin and Herrlich, 1989; Ronai et al, 1990; Holbrook and Fornance, 1991; Herrlich et al, 1992).


Pp42 MAPK bZip Region Transdominant Negative Mutant 
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  1. Abate C, Patel L, Rauscher III FJ, Curran T (1990): Redox regulation of Fos and Jun DNA-binding activity in vitro. Science 249: 1157–1161PubMedGoogle Scholar
  2. Ackermann P, Osheroff N (1989): Regulation of casein kinase II activity by epidermal growth factor in human A-432 carcinoma cells. J Biol Chem 264: 11958–11965Google Scholar
  3. Adler V, Polotskaya A, Wagner F, Kraft AS (1992): Affinity-purified c-Jun amino-terminal protein kinase requires serine/threonine phosphorylation for activity.J Biol Chem 267: 17001–17005PubMedGoogle Scholar
  4. Alani R, Brown P, Binétruy B, Dosaka H, Rosenberg RK, Angel P, Karin M, Birrer MJ (1991): The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells. Mol Cell Biol 11: 6286–6295PubMedGoogle Scholar
  5. Allison AC (1988): Immunopathogenic Mechanisms of Arthritis. Goodacre J, Diek WC, eds. Boston: MIT PressGoogle Scholar
  6. Angel P, Karin M (1991): The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochem Biophys Acta 1072: 129–157PubMedGoogle Scholar
  7. Angel P, Baumann I, Stein B, Delius H, Rahmsdorf H J, Herrlich P (1987b): 12–0-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5’-flanking region. Mol Cell Biol 7: 2256–2266PubMedGoogle Scholar
  8. Angel P, Hattori K, Smeal T, Karin M (1988): The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell 55: 875–885PubMedGoogle Scholar
  9. Angel P, Smeal T, Meek J, Karin M (1989): Jun and v-Jun contain multiple regions that participate in transcriptional activation in an interdependent manner. New Biol 1:35–43PubMedGoogle Scholar
  10. Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M (1987a): Phorbol ester-inducible genes contain a common eis element recognized by a TPA-modulated trans-acting factor. Cell 49: 729–739PubMedGoogle Scholar
  11. Angel P, Pöting A, Mallick U, Rahmsdorf HJ, Schorpp M, Herrlich P (1986): Induction of metallothionein and other mRNA species by carcinogens and tumor promoters in primary human skin fibroblasts. Mol Cell Biol 6: 1760–1766PubMedGoogle Scholar
  12. Auwerx J, Sassone-Corsi P (1991): IP-1: a dominant inhibitor of Fos/Jun whose activity is modulated by phosphorylation. Cell 64: 983–993PubMedGoogle Scholar
  13. Baeuerle PA (1991): The inducible transcription factor NF-κB: Regulation by distinct protein subunits. Biochim Biophys Acta 1072: 63–80PubMedGoogle Scholar
  14. Baichwal VR, Tjian R (1990): Control of cJun activity by interaction of a cell-specific inhibitor. Cell 63: 815–825PubMedGoogle Scholar
  15. Baichwal VR, Park A, Tjian R (1991): v-Src and EJ Ras alleviate repression of c-Jun by a cell-specific inhibitor. Nature 352: 165–168PubMedGoogle Scholar
  16. Barbacid M (1986): Mutagenes, oncogenes and cancer. TIG 2: 188–192Google Scholar
  17. Bauknecht T, Angel P, Royer HD, zur Hausen H (1992): Identification of a negative regulatory domain in the human papillomavirus type 18 promoter: interaction with the transcriptional repressor YY1. EMBO 7 11: 4607–4617Google Scholar
  18. Bauknecht T, Angel P, Kohler M, Kommoss F, Birmelin G, Pfleiderer A, Wagner A (1993): Gene structure and expression analysis of the epidermal growth factor receptor, transforming growth factor-alpha, myc, jun and metallothionein in human ovarian carcinomas. Cancer 71: 419–429PubMedGoogle Scholar
  19. Belman S, Troll W (1972): The inhibition of croton oil-promoted mouse skin tumorigenesis by steroid hormones. Cancer Res 32: 450–454PubMedGoogle Scholar
  20. Benbrook DM, Jones NC (1990): Heterodimer formation between CREB and JUN proteins. Oncogene 5: 295–302PubMedGoogle Scholar
  21. Bengal E, Ransone L, Scharfmann R, Dwarki VJ, Tapscot SJ, Weintraub H, Verma IM (1992): Functional antagonism between c-Jun and MyoD proteins: a direct physical association. Cell 68: 507–519PubMedGoogle Scholar
  22. Bergelson S, Pinkus R, Daniel V (1994): Induction of AP-1 (Fos/Jun) by chemical agents mediates activation of glutathione S-transferase and quinone reductase gene expression. Oncogene 9: 565–571PubMedGoogle Scholar
  23. Betsholtz C, Johnsson A, Heldin C-H, Westermark B (1986): Efficient reversion of simian sarcoma virus-transformation and inhibition of growth factor-induced mitogenesis by suramin. Proc Natl Acad Sci USA 83: 6440–6444PubMedGoogle Scholar
  24. Binétruy B, Smeal T, Karin M (1991): Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. Nature 351: 122–127PubMedGoogle Scholar
  25. Black EJ, Street AJ, Gillespie DAF (1991): Protein phosphatase 2A reverses phosphorylation of c-Jun specified by the delta domain in vitro: correlation with oncogenic activation and regulated transactivation activity. Oncogene 6: 1949–1958PubMedGoogle Scholar
  26. Blenis J (1993): Signal transduction via the MAP kinases: Proceed at your own RSK. Proc Natl Acad Sci USA 90: 5889–5892PubMedGoogle Scholar
  27. Bohmann D (1994): personal communicationGoogle Scholar
  28. Bohmann D, Tjian R (1989): Biochemical analysis of transcriptional activation by Jun: differential activity of c- and v-Jun. Cell 59: 709–717PubMedGoogle Scholar
  29. Boyle WJ, Smeal T, Defize LHK, Angel P, Woodgett JR, Karin M, Hunter T (1991): Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity. Cell 64: 573–584PubMedGoogle Scholar
  30. Busch SJ, Sassone-Corsi P (1990): Dimers, leucine-zippers and DNA binding domains. TIG 6: 36–40PubMedGoogle Scholar
  31. Büscher M, Rahmsdorf HJ, Litfin M, Karin M, Herrlich P (1988): Activation of the c-fos gene by UV and phorbol ester: different signal transduction pathways converge to the same enhancer element. Oncogene 3: 301–311PubMedGoogle Scholar
  32. Carroll D, Santoro N, Marshak DR (1988): Regulating cell growth: casein kinase II-dependent phosphorylation of nuclear oncoproteins. Cold Spring Harbor Symp Quant Biol 53: 91–95PubMedGoogle Scholar
  33. Catellazzi M, Spyrou G, La V, Dangy J, Piu F, Yaniv M, Brun G (1991): Over-expression of c-jun, junB, or junD affects cell growth differently. Proc Natl Acad Sci USA 88: 8890–8894Google Scholar
  34. Cerutti PA (1985): Prooxidant states and tumor promotion. Science 227: 375–381PubMedGoogle Scholar
  35. Cerutti PA, Trump BF (1991): Inflammation and oxidative stress in carcinogenesis. Cancer Cells 3: 1–7PubMedGoogle Scholar
  36. Chida K, Vogt PK (1992): Nuclear translocation of viral Jun but not of cellular Jun is cell cycle dependent. Proc Natl Acad Sci USA 89: 4290–4294PubMedGoogle Scholar
  37. Chiu R, Angel P, Karin M (1989): Jun-B differs in its biological properties from, and is a negative regulator of, cJun. Cell 59: 979–986PubMedGoogle Scholar
  38. Cobb MH, Boulton TG, Robbins DJ (1991): Extracellular signal-regulated kinases-ERKs in progress. Cell Reg 2: 965–978Google Scholar
  39. Coffey Jr, RJ, Leof EB, Shipley GD, Moses HL (1987): Suramin inhibition of growth factor receptor binding and mitogenicity in AKR-2B cells. J Cell Physiol 132: 143–148PubMedGoogle Scholar
  40. Cohen DR, Curran T (1990): Analysis of dimerization and DNA binding functions in Fos and Jun by domain-swapping: involvement of residues outside the leucine zipper/basic region. Oncogene 5: 929–939PubMedGoogle Scholar
  41. Curran T, Franza Jr, BR (1988): Fos and Jun: The AP-1 connection. Cell 55: 395–397PubMedGoogle Scholar
  42. de Groot RP, Auwerx J, Karperien M, Staels B, Kruijer W (1991a): Activation of junB by PKC and PKA signal transduction through a novel cis-acting element. Nucleic Acids Res 19: 775–781PubMedGoogle Scholar
  43. de Groot RP, Karperien M, Pals C, Kruijer W (1991b): Characterization of the mouse junD promoter-high basal level activity due to an octamer motif. EMBO J 10: 2523–2532PubMedGoogle Scholar
  44. de Groot RP, Auwerx J, Bourouis M, Sassone-Corsi P (1993): Negative regulation of Jun/AP-1: conserved function of glycogen synthase kinase 3 and the Drosophila kinase shaggy. Oncogene 8: 841–847PubMedGoogle Scholar
  45. Deng T, Karin M (1993): JunB differs from c-Jun in its DNA-binding and dimerization domains, and represses c-Jun by formation of inactive heterodimers. Genes Dev 7: 479–490PubMedGoogle Scholar
  46. Devary Y, Gottlieb RA, Lau LF, Karin M (1991): Rapid and preferential activation of the c-jun gene during the mammalian UV response. Mol Cell Biol 11: 2804–2811PubMedGoogle Scholar
  47. Devary Y, Gottlieb RA, Smeal T, Karin M (1992): The mammalian ultraviolet response is triggered by activation of Src tyrosine kinases. Cell 71: 1081–1091PubMedGoogle Scholar
  48. Devary Y, Rosette C, DiDonato JA, Karin M (1993): NF-/cB activation by ultraviolet light not dependent on a nuclear signal. Science 261: 1442–1445PubMedGoogle Scholar
  49. Diamond MI, Miner JN, Yoshinaga SK, Yamamoto KR (1990): Transcription factor interactions: Selectors of positive or negative regulation from a single DNA element. Science 249: 1266–1272PubMedGoogle Scholar
  50. Franklin CC, Sanchez V, Wagner F, Woodgett JR, Kraft AS (1992): Phorbol ester-induced amino-terminal phosphorylation of human JUN but not JUNB regulates transcriptional activation. Proc Natl Acad Sci USA 89: 7247–7251PubMedGoogle Scholar
  51. Friling RS, Bergelson S, Daniel V (1992): Two adjacent AP-1-like binding sites form the electrophile-responsive element of the murine glutathione S-transferase Ya subunit gene. Proc Natl Acad Sci USA 89: 668–672PubMedGoogle Scholar
  52. Gaub M-P, Bellard M, Scheuer I, Chambon P, Sassone-Corsi P (1990): Activation of the ovalbumin gene by the estrogen receptor involves the Fos-Jun complex. Cell 63: 1267–1276PubMedGoogle Scholar
  53. Gentz R, Rauscher III FJ, Abate C, Curran T (1989): Parallel association of Fos and Jun leucine zippers juxtaposes DNA binding domains. Science 243: 1695–1699PubMedGoogle Scholar
  54. Grigoriadis AE, Schellander K, Wang Z-Q, Wagner EF (1993): Osteoblasts are target cells for transformation in c-fos transgenic mice. J Cell Biol 122: 685–701PubMedGoogle Scholar
  55. Hagmeyer BM, König H, Herr I, Offringa R, Zantema A, van der Eb AJ, Herrlich P, Angel P (1993): Adenovirus El A negatively and positively modulates transcription of AP-1 dependent genes by dimer-specific regulation of the DNA binding and transactivation activities of Jun. EMBO J 12: 3559–3572PubMedGoogle Scholar
  56. Hai T, Curran T (1991): Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci USA 88: 3720–3724PubMedGoogle Scholar
  57. Hashimoto Y, Tajima O, Hashiba H, Nose K, Kuroki T (1990): Elevated expression of secondary, but not early, responding genes to phorbol ester tumor promoters in papillomas and carcinomas of mouse skin. Mol Carcinog 3: 302–308PubMedGoogle Scholar
  58. Herr I, van Dam H, Angel P (1994): Binding of promoter-associated AP-1 is not altered during induction and subsequent repression of the c-jun promoter by TPA and UV irradiation. Carcinogenesis 15: 1105–1113PubMedGoogle Scholar
  59. Herrera R, Ro HS, Robinson GS, Xanthopoulos KG, Spiegelman (1989): A direct role for C/EBP and the AP-1-binding site in gene expression linked to adipocyte differentiation. Mol Cell Biol 9: 5331–5339PubMedGoogle Scholar
  60. Herrlich P, Ponta H (1989): “Nuclear” oncogenes convert extracellular stimuli into changes in the genetic program. TIG 5: 112–116PubMedGoogle Scholar
  61. Herrlich P, Ponta H, Rahmsdorf HJ (1992): DNA damage-induced gene expression: signal transduction and relation to growth factor signaling. Rev of Physiol Biochem Pharmacol 119: 187–223Google Scholar
  62. Hibi M, Lin A, Smeal T, Minden A, Karin M (1993): Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes & Dev 7: 2135–2148Google Scholar
  63. Hirai S-I, Ryseck R-P, Mechta F, Bravo R, Yaniv M (1989): Characterization of junD: a new member of the jun proto-oncogene family. EMBO J 8: 1433–1439PubMedGoogle Scholar
  64. Hirai S-I, Bourachot B, Yaniv M (1990): Both Jun and Fos contribute to transcription activation by the heterodimer. Oncogene 5: 39–46PubMedGoogle Scholar
  65. Hofmann M, Rudy W, Günthert U, Zimmer SG, Zawadzki V, Zöller M, Lichtner RB, Herrlich P, Ponta H (1993): A link between RAS and metastatic behavior of tumor cells: ras induces CD44 promoter activity and leads to low-level expression of metastasis-specific variants of CD44 in CREF cells. Cancer Res 53: 1516–1521PubMedGoogle Scholar
  66. Holbrook NJ, Fornace Jr, AJ (1991): Response to adversity: molecular control of gene activation following genotoxic stress. New Biol 3: 825–833PubMedGoogle Scholar
  67. Hunter T, Karin M (1992): Control of transcription factor activity by protein phosphorylation. Cell 70: 375–388PubMedGoogle Scholar
  68. Jackson SP, Tjian R (1988): O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation. Cell 55: 125–133PubMedGoogle Scholar
  69. Johnson RS, Spiegelman BM, Papaioannou V (1992): Pleiotropic effects of a null mutation in the c-fos proto-oncogene. Cell 71: 577–586PubMedGoogle Scholar
  70. Jonat C, Rahmsdorf HJ, Park K-K, Cato ACB, Gebel S, Ponta H, Herrlich P (1990): Anti-tumor promotion and antiinflammation: Down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell 62: 1189–1204PubMedGoogle Scholar
  71. Kaina B, Lohrer H, Karin M, Herrlich P (1990): Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents. Proc Natl Acad Sci USA 87: 2710–2714PubMedGoogle Scholar
  72. Karin M (1985): Metallothioneins: proteins in search of function. Cell 41: 9–10PubMedGoogle Scholar
  73. Karin M, Herrlich P (1989): Cis- and trans-acting genetic elements responsible for induction of specific genes by tumor promoters, serum factors, and stress. In: Genes and Signal Transduction in Multistage Carcinogenesis, Colburn NH ed. New York-Basel: Marcel DekkerGoogle Scholar
  74. Karin M, Smeal T (1992): Control of transcription factors by signal transduction pathways: The beginning of the end. TIBS 17: 418–422PubMedGoogle Scholar
  75. Kelley SL, Basu A, Teicher BA, Hacker MP, Hamer DH, Lazo JS (1988): Overexpression of metallothionein confers resistance to anticancer drugs. Science 241: 1813–1815PubMedGoogle Scholar
  76. Kölch W, Heidecker G, Kochs G, Hummel R, Vahidi H, Mischak H, Finkenzeller G, Marmè D, Rapp UR (1993). Protein kinase Cα activates RAF-1 by direct phosphorylation. Nature 364: 249–252PubMedGoogle Scholar
  77. König H, Ponta H, Rahmsdorf HJ, Herrlich P (1992): Interference between pathway-specific transcription factors: glucocorticoids antagonize phorbol ester-induced AP-1 activity without altering AP-1 site occupation in vivo. EMBO J 11: 2241–2246PubMedGoogle Scholar
  78. Koo AS, Chiu R, Soong J, deKernion JB, Belldegrun A (1992): The expression of c-jun and junB mRNA in renal cell cancer and in vitro regulation by transforming growth factor beta 1 and tumor necrosis factor alpha 1. J Urol 148: 1314–1318PubMedGoogle Scholar
  79. Kouzarides JT, Ziff E (1988): Role of the leucine zipper in the fos-jun interaction. Nature 336: 646–651PubMedGoogle Scholar
  80. Kouzarides T, Ziff E (1989): Leucine zippers of fos, jun and GCN4 dictate dimerization specificity and thereby control DNA binding. Nature 340: 568–571PubMedGoogle Scholar
  81. Kovary K, Bravo R (1991): The Jun and Fos protein families are both required for cell cycle progression in fibroblasts. Mol Cell Biol 11: 4466–4472PubMedGoogle Scholar
  82. Krämer M, Sachsenmaier C, Herrlich P, Rahmsdorf HJ (1993): UV-irradiation-induced interleukin-1 and basic fibroblast growth factor synthesis and release mediate part of the UV response. J Biol Chem 268: 6734–6741PubMedGoogle Scholar
  83. Kyriakis JM, App H, Zhang X, Banerjee P, Brautigan DL, Rapp UR, Avruch J (1992): Raf-1 activates MAP kinase-kinase. Nature 358: 417–421PubMedGoogle Scholar
  84. Landschulz WH, Johnson PF, McKnight SL (1988): The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science 240: 1759–1764PubMedGoogle Scholar
  85. Lee W, Haslinger A, Karin M, Tjian R (1987a): Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature 325: 368–372PubMedGoogle Scholar
  86. Lee W, Mitchell P, Tjian R (1987b): Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell 49: 741–752PubMedGoogle Scholar
  87. Li L, Chambard JC, Karin M, Olson EC (1992): Fos and Jun repress transcriptional activation by myogenin and MyoD: the amino terminus of Jun can mediate repression. Genes Dev 6: 676–689PubMedGoogle Scholar
  88. Li Y, Jaiswal AK (1992): Regulation of human NAD(P)H:quinone oxireductase gene.J Biol Chem 267: 15097–15104PubMedGoogle Scholar
  89. Lin A, Frost J, Deng T, Smeal T, Al-Alawi N, Kikkawa U, Hunter T, Brenner D, Karin M (1992): Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity. Cell 70: 777–789PubMedGoogle Scholar
  90. Little JW, Mount DW (1982): The SOS regulatory system of Escherichia coli. Cell 29: 11–22Google Scholar
  91. Lloyd A, Yancheva N, Wasylyk B (1991): Transformation suppressor activity of a Jun transcription factor lacking its activation domain. Nature 352: 635–638PubMedGoogle Scholar
  92. Maki Y, Bos TJ, Davis C, Starbuck M, Vogt PK (1987): Avian sarcoma virus 17 carries the jun oncogene. Proc Natl Acad Sci USA 84: 2848–2852PubMedGoogle Scholar
  93. Miner JN, Diamond MI, Yamamoto KR (1991): Joints in the regulatory lattice: composite regulation by steroid receptor AP-1 complexes. Cell Growth Diff 2: 525–530PubMedGoogle Scholar
  94. Minna JD, Schütte J, Viallet J, Thomas F, Kaye FJ, Takahashi T, Nau M, Whang-Peng J, Birrer M, Gazdar AF (1989): Transcription factors and recessive oncogenes in the pathogenesis of human lung cancer. Int J Cancer Suppl 4: 32–34PubMedGoogle Scholar
  95. Morgan IM, Asano M, Havarstein LS, Ishikawa H, Hiiragi T, Ito Y, Vogt PK (1993): Amino acid substitutions modulate the effect of Jun on transformation, transcriptional activation and DNA replication. Oncogene 8: 1135–1140PubMedGoogle Scholar
  96. Müller R, Slamon DJ, Tremblay JM, Cline MJ, Verma IM (1982): Differential expression of cellular oncogenes during pre- and postnatal development of the mouse. Nature 299: 640–644PubMedGoogle Scholar
  97. Nakagawa K, Saijo N, Tsuchida S, Sakai M, Tsunokawa Y, Yokata J, Muramatsu M, Sato K, Terada M, Tew KD (1990): Glutathione-S-transferase pi as a determinant of drug resistance in transfectant cell lines. J Biol Chem 265: 4296–4301PubMedGoogle Scholar
  98. Neuberg M, Adamkiewicz J, Hunter JB, Müller R (1989a): A Fos protein containing the Jun leucine zipper forms a homodimer which binds to the API binding site. Nature 341: 243–245PubMedGoogle Scholar
  99. Neuberg, M, Schuermann M, Hunter JB, Müller R (1989b): Two functionally different regions in Fos are required for the sequence-specific DNA interaction of the Fos/Jun protein complex. Nature 338: 589–590PubMedGoogle Scholar
  100. Oehler T, Angel P (1993): unpublished observationGoogle Scholar
  101. Oehler T, Angel P (1992): A common intermediary factor (p52/54) recognizing “acidic-blob”-type domains is required for transcriptional activation by the Jun proteins. Mol Cell Biol 12: 5508–5515PubMedGoogle Scholar
  102. Oehler T, Pintzas A, Stumm S, Darling A, Gillespie D, Angel P (1993): Mutation of a phosphorylation site in the DNA binding domain is required for redox-independent transactivation of API-dependent genes by v-Jun. Oncogene 8: 1141–1147PubMedGoogle Scholar
  103. Offringa R, Gebel S, van Dam H, Timmers M, Smits A, Zwart R, Stein B, Bos JL, van der Eb A, Herrlich P (1990): A novel function of the transforming domain of Ela: repression of AP-1 activity. Cell 62: 527–538PubMedGoogle Scholar
  104. Offringa R, Smits AMM, Houweling A, Bos JL, van der Eb AJ (1988): Similar effects of adenovirus Ela and glucocorticoid hormones on the expression of the metalloprotease stromelysin. Nucleic Acids Res 16: 10973–10984PubMedGoogle Scholar
  105. Okuda A, Imagawa M, Sakai M, Muramatsu M (1990): Functional cooperativity between two TPA responsive elements in undifferentiated F9 embryonic stem cells. EMBO J 9: 1131–1135PubMedGoogle Scholar
  106. Oliviero S, Robinson GS, Struhl K, Spiegelman BM (1992): Yeast GCN4 as a probe for oncogenesis by AP-1 transcription factors: transcriptional activation through AP-1 sites is not sufficient for cellular transformation. Genes Dev 6: 1799–1809PubMedGoogle Scholar
  107. O’Shea E, Rutkowski R, Kim PS (1989): Evidence that the leucine zipper is a coiled coil. Science 243: 538–542PubMedGoogle Scholar
  108. Ostrowski LE, Finch J, Krieg P, Matrisian L, Patskan G, O’Connell JF, Phillips J, Slaga TJ, Breathnach R, Bowden GT (1988): Expression pattern of a gene for a secreted metalloproteinase during late stages of tumor progression. Molec Carcinogenesis 1: 13–19Google Scholar
  109. Papavassiliou AG, Chavrier C, Bohmann D (1992): Phosphorylation state and DNA-binding activity of cJun dependent on the intracellular concentration of binding sites. Proc Natl Acad Sci USA 89: 11562–11565PubMedGoogle Scholar
  110. Payne DM, Rossomando AJ, Martino P, Erickson AK, Her J-H, Shabanowitz J, Hunt DF, Weber MJ, Sturgill TW (1991): Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase). EMBO J 10: 885–892PubMedGoogle Scholar
  111. Pelech SL, Sanghere JS (1992): MAP kinases: Charting the regulatory pathways. Science 257: 1355–1356PubMedGoogle Scholar
  112. Pfarr CM, Mechta F, Spyrou G, Lallemand D, Carillo S, Yaniv M (1994): Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell 76: 747–760PubMedGoogle Scholar
  113. Ponta H, Cato ACB, Herrlich P (1992): Interference of pathway specific transcription factors. Biochim Biophys Acta 1129: 255–261PubMedGoogle Scholar
  114. Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR (1991): Phosphorylation of c-jun mediated by MAP kinases. Nature 353: 670–674PubMedGoogle Scholar
  115. Pulverer BJ, Hughes K, Franklin CC, Kraft AS, Leevers S J, Woodgett JR (1992): Copurification of mitogen-activated protein kinases with phorbol ester-induced c-Jun kinase activity in U937 leukaemic cells. Oncogene 7: 407–415Google Scholar
  116. Quantin B, Breathnach R (1988): Epidermal growth factor stimulates transcription of the c-jun proto-oncogene in rat fibroblasts. Nature 334: 538–539PubMedGoogle Scholar
  117. Radler-Pohl A, Sachsenmaier C (1994): unpublished observationGoogle Scholar
  118. Radler-Pohl A, Sachsenmaier C, Gebel S, Auer H-P, Bruder JT, Rapp U, Angel P, Rahmsdorf HJ, Herrlich P (1993a): UV-induced activation of AP-1 involves obligatory extranuclear steps including Raf-1 kinase. EMBO J 12: 1005–1012PubMedGoogle Scholar
  119. Radler-Pohl A, Gebel S, Sachsenmaier C, König H, Krämer M, Oehler T, Streile M, Ponta H, Rapp U, Rahmsdorf H, Cato ACB, Angel P, Herrlich P (1993b): The activation and activity control of AP-1 (Fos/Jun). In: Annals of the New York Academy of Sciences, vol 684, M. Sluyser, G. Ab, A.O. Brinkman, R.A. Blankenstein, pp. 127–148. Meeting on “Zinc Finger Proteins in Oncogenesis: DNA binding and gene regulation”Google Scholar
  120. Ransone LJ, Visvader J, Wamsley P, Verma IM (1990): Trans-dominant negative mutants of Fos and Jun. Proc Natl Acad Sci USA 87: 3806–3810PubMedGoogle Scholar
  121. Ronai ZA, Lambert ME, Weinstein IB (1990): Inducible cellular responses to ultraviolet light irradiation and other mediators of DNA damage in mammalian cells. Cell Biol Toxicol 6: 105–126PubMedGoogle Scholar
  122. Rozek D, Pfeifer GP (1993): In vivo protein-DNA interactions at the c-jun promoter: preformed complexes mediate the UV response. Mol Cell Biol 13: 5490–5499PubMedGoogle Scholar
  123. Ryder K, Lanahan A, Perez-Albuerne E, Nathans D (1989): Jun-D: a third member of the Jun gene family. Proc Natl Acad Sci USA 86: 1500–1503PubMedGoogle Scholar
  124. Ryder K, Lau LF, Nathans D (1988): A gene activated by growth factors is related to the oncogene v-jun. Proc Natl Acad Sci USA 85: 1487–1491PubMedGoogle Scholar
  125. Ryseck RP, Bravo R (1991): cJun, JunB and JunD differ in their binding affinities to AP-1 and CRE consensus sequences: effect of Fos proteins. Oncogene 6: 533–542PubMedGoogle Scholar
  126. Ryseck R-P, Hirai SI, Yaniv M, Bravo R (1988): Transcriptional activation of c-jun during the G0/Gi transition in mouse fibroblasts. Nature 334: 535–537PubMedGoogle Scholar
  127. Sachsenmaier C, Radler-Pohl A, Zinck R, Nordheim A, Herrlich P, Rahmsdorf HJ (1994): Involvement of growth factor receptors in the mammalian UVC response. Cell in pressGoogle Scholar
  128. Sakai M, Muramatsu M, Nishi S (1992): Suppression of glutathione transferase P expression by glucocorticoids. Biochem Biophys Res Comm 187: 976–983PubMedGoogle Scholar
  129. Sassone-Corsi P, Ransone LJ, Lamph WW, Verma IM (1988): Direct interaction between fos and jun nuclear oncoproteins: role of the “leucine zipper” domain. Nature 336: 692–695PubMedGoogle Scholar
  130. Schönthal A, Herrlich P, Rahmsdorf HJ, Ponta H (1988): Requirement for fos gene expression in the transcriptional activation of collagenase by other oncogenes and phorbol esters. Cell 54: 325–334PubMedGoogle Scholar
  131. Schönthal A, Alberts AS, Fost JA, Feramisco JR (1991): Differential regulation of jun family gene expression by the tumor promoter okadaic acid. New Biol 3: 977–986PubMedGoogle Scholar
  132. Schorpp M, Mallick U, Rahmsdorf, HJ, Herrlich P (1984): UV-induced extracellular factor from human fibroblasts communicates the UV response to nonirradiated cells. Cell 37: 861–868PubMedGoogle Scholar
  133. Schreck R, Baeuerle PA (1991): A role for oxygen radicals as second messengers. Trends Cell Biol 1:39–42PubMedGoogle Scholar
  134. Schuh AC, Keating SJ, Monteclaro FS, Vogt PK, Breitman ML (1990): Obligatory wounding requirement for tumorigenesis in v-jun transgenic mice. Nature 346: 756–760PubMedGoogle Scholar
  135. Schüle R, Rangarajan P, Kliewer S, Ransone LJ, Bolado J, Yang N, Verma IM, Evans RM (1990a): Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell 62: 1217–1226PubMedGoogle Scholar
  136. Schüle R, Umesono K, Mangelsdorf DJ, Bolado J, Pike JW, Evans RM (1990b): Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene. Cell 61: 497–504PubMedGoogle Scholar
  137. Schüle R, Evans RM (1991): Cross-coupling of signal tranduction pathways: zinc finger meets leucine zipper. TIG 7: 377–381PubMedGoogle Scholar
  138. Schütte J, Minna JD, Birrer MJ (1989a): Deregulated expression of human c-jun transforms primary rat embryo cells in cooperation with an activated c-Ha-ras gene and transforms Rat-la cells as a single gene. Proc Natl Acad Sci USA 86: 2257–2261PubMedGoogle Scholar
  139. Schütte J, Viallet J, Nau M, Segal S, Fedorko J, Minna J (1989b): Jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell 59: 987–997PubMedGoogle Scholar
  140. Scribner JD, Slaga TJ (1973): Multiple effects of dexamethasone on protein synthesis and hyperplasia caused by a tumor promoter. Cancer Res 33: 542–546PubMedGoogle Scholar
  141. Sellers JW, Struhl K (1989): Changing Fos oncoprotein to a Jun-independent DNA-binding protein with GCN4 dimerization specificity by swapping ‘leucine zipper’. Nature 341: 74–76PubMedGoogle Scholar
  142. Smeal T, Binétruy B, Mercola DA, Birrer M, Karin M (1991): Oncogenic and transcriptional cooperation and Ha-ras requires phosphorylation of c-Jun on serines 63 and 73. Nature 354: 494–496PubMedGoogle Scholar
  143. Smeal T, Binétruy B, Mercola D, Grover-Bardwick A, Heidecker G, Rapp, UR, Karin M (1992): Oncoprotein mediated signalling cascade stimulates cJun activity by phosphorylation of serines 63 and 73. Mol Cell Biol 12: 3507–3513PubMedGoogle Scholar
  144. Stein B, Angel P, van Dam H, Ponta H, Herrlich P, van der Eb A, Rahmsdorf HJ (1992): Ultraviolet-radiation induced c-jun gene transcription: two AP-1 like binding sites mediate the response. Photochem Photobiol 55: 409–415PubMedGoogle Scholar
  145. Stein B, Baldwin Jr AS, Ballard DW, Greene WC, Angel P, Herrlich P (1993): Crosscoupling of the NF-kB p65 and Fos/Jun transcription factors produces potentiated biological function. EMBO J 12: 3879–3891PubMedGoogle Scholar
  146. Stein B, Rahmsdorf HJ, Steffen A, Litfin M, Herrlich P (1989): UV-induced DNA damage is an intermediate step in UV-induced expression of human immunodeficiency virus type 1, collagenase, c-fos, and metallothionein. Mol Cell Biol 9: 5169–5181PubMedGoogle Scholar
  147. Toftgard R, Roop DR, Yuspa SH (1985): Protooncogene expression during two-stage carcinogenesis in mouse skin. Carcinogenesis 6: 655–657PubMedGoogle Scholar
  148. Tratner I, Verma IM (1991): Identification of a nuclear targeting sequence in the Fos protein. Oncogene 6: 2049–2053PubMedGoogle Scholar
  149. Turner R, Tjian R (1989): Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cFos-cJun heterodimers. Science 243: 1689–1694PubMedGoogle Scholar
  150. Unlap T, Franklin CC, Wagner F, Kraft AS (1992): Upstream regions of the c-jun promoter regulate phorbol ester-induced transcription in U937 leukemic cells. Nucleic Acids Res 20: 897–902PubMedGoogle Scholar
  151. van Beveren C, van Straaten F, Curran T, Müller R, Verma IM (1983): Analysis of FBJ-MuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini. Cell 32: 1241–1255PubMedGoogle Scholar
  152. van Dam H, Duyndam M, Rottier R, Bosch A, de Vries-Smits L, Herrlich P, Zantema A, Angel P, van der Eb AJ (1993): Heterodimer formation of cJun and ATF-2 is responsible for induction of c-jun by the 243 amino acid adenovirus Ela protein. EMBO J 12: 479–487PubMedGoogle Scholar
  153. van Dam H, Offringa R, Meijer I, Stein B, Smits AM, Herrlich P, Bos JL, van der Eb AJ (1990): Differential effects of the adenovirus Ela oncogene on members of the AP-1 transcription factor family. Mol Cell Biol 10: 5857–5864PubMedGoogle Scholar
  154. van den Berg S, Kaina B, Rahmsdorf HJ, Ponta H, Herrlich P (1991): Involvement of Fos in spontaneous and ultraviolet light induced genetic changes. Molec Carcinogenesis 4: 460–466Google Scholar
  155. van Straaten F, Müller R, Curran T, van Beveren C, Verma IM (1983): Complete nucleotide sequence of a human c-onc gene: deduced amino acid sequence of the human c-fos protein. Proc Natl Acad Sci USA 80: 3183–3187PubMedGoogle Scholar
  156. Vogt PK, Bos TJ (1990): Jun: Oncogene and transcription factor. Adv Cancer Res 55: 1–35PubMedGoogle Scholar
  157. Walker GC (1985): Inducible DNA repair systems. Ann Rev Biochem 54: 425–457PubMedGoogle Scholar
  158. Wang Z-Q, Ovitt C, Grigoriadis AE, Möhle-Steinlein U, Rüther, U, Wagner EF (1992): Bone and haematopoietic defects in mice lacking c-fos. Nature 360: 741PubMedGoogle Scholar
  159. Wood KW, Sarnecki C, Roberts TM, Blenis J (1992): Ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP-kinase, Raf-1, and RSK. Cell 68: 1041–1050PubMedGoogle Scholar
  160. Xanthoudakis S, Curran T (1992): Identification and characterization of Ref-1, a nuclear protein that facilities AP-1 DNA-binding activity. EMBO J 11: 653–665PubMedGoogle Scholar
  161. Yang-Yen H-F, Chambard J-C, Sun Y-L, Smeal T, Schmidt TJ, Drouin J, Karin M (1990): Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell 62: 1205–1215PubMedGoogle Scholar
  162. Zhang X-K, Dong J-M, Chiu J-F (1991): Regulation of α-fetoprotein gene expression by antagonism between AP-1 and the glucocorticoid receptor at their overlapping bind site.J Biol Chem 266: 8248–8254PubMedGoogle Scholar
  163. Zhang X, Settlerman J, Kyriakis JM, Suzuki E, Elledge J, Marshall M, Bruder J, Rapp UR, Avruch J (1993): Normal and oncogenic p21ras proteins binds to the amino terminal regulatory domain of c-Raf-1. Nature 364: 308–313PubMedGoogle Scholar

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© Birkhäuser Boston 1995

Authors and Affiliations

  • Peter Angel

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