AP-1: A double-edged sword in tumorigenesis

Nature Reviews Cancer

Volumn 3, Issue 11, 2003, Pages 859-868

  Eferl, Robert ^a   Wagner, Erwin F ^a  

^a RESEARCH INSTITUTE OF MOLECULAR PATHOLOGY   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR; PROTEIN C JUN; PROTEIN FOS; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR MAF; UNCLASSIFIED DRUG;

CANCER INHIBITION; CARCINOGENESIS; CARCINOGENICITY; CELL PROLIFERATION; GENE TARGETING; NONHUMAN; ONCOGENE C FOS; ONCOGENE C JUN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; TUMOR CELL; TUMOR SUPPRESSOR GENE;

EID: 0242691046     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc1209     Document Type: Review

References (83)

1. AP-1. Oncogene 20 (issue 19) (2001).
2. Chinenov, Y. & Kerppola, T. K. Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity. Oncogene 20, 2438-2452 (2001).
3. Vogt, P. K. Fortuitous convergences: the beginnings of JUN. Nature Rev. Cancer 2, 465-469 (2002).
4. Angel, P. & Karin, M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim. Biophys. Acta 1072, 129-157 (1991).
5. Jochum, W., Passegue, E. & Wagner, E. F. AP-1 in mouse development and tumorigenesis. Oncogene 20, 2401-2412 (2001).
6. Wang, Z. Q., Grigoriadis, A. E., Mohle-Steinlein, U. & Wagner, E. F. A novel target cell for c-fos-induced oncogenesis: development of chondrogenic tumours in embryonic stem cell chimeras. EMBO J. 10, 2437-2450 (1991).
7. Grigoriadis, A. E., Schellander, K., Wang, Z. Q. & Wagner, E. F. Osteoblasts are target cells for transformation in c-fos transgenic mice. J. Cell Biol. 122, 685-701 (1993).
8. Young, M. R. et al. Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion. Proc. Natl Acad. Sci. USA 96, 9827-9832 (1999).
9. Eferl, R. et al. Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53. Cell 112, 181-192 (2003). This study genetically links c-Jun and p53 activities in liver tumorigenesis in vivo.
10. Bergers, G., Graninger, P., Braselmann, S., Wrighton, C. & Busslinger, M. Transcriptional activation of the fra-1 gene by AP-1 is mediated by regulatory sequences in the first intron. Mol. Cell. Biol. 15, 3748-3758 (1995).
11. Foletta, V. C. et al. Cloning and characterisation of the mouse fra-2 gene. Oncogene 9, 3305-3311 (1994).
12. Vandel, L. et al. Increased transforming activity of JunB and JunD by introduction of an heterologous homodimerization domain. Oncogene 10, 495-507 (1995).
13. Jochum, W. et al. Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1. Nature Med. 6, 980-984 (2000).
14. Deng, T. & Karin, M. JunB differs from c-Jun in its DNA-binding and dimerization domains, and represses c-Jun by formation of inactive heterodimers. Genes Dev. 7, 479-490 (1993).
15. Chiu, R., Angel, P. & Karin, M. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Cell 59, 979-986 (1989).
16. Passegue, E., Jochum, W., Schorpp-Kistner, M., Mohle-Steinlein, U. & Wagner, E. F. Chronic myeloid leukemia with increased granulocyte progenitors in mice lacking junB expression in the myeloid lineage. Cell 104, 21-32 (2001). Clearly shows the tumour-suppressor activity of JunB in in vivo models of myeloid leukaemia.
17. Zenz, R. et al. c-Jun regulates eyelid closure and skin tumor development through EGFR signaling. Dev. Cell 4, 879-889 (2003).
18. Pfarr, C. M. et al. Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell 76, 747-760 (1994). This excellent study dissects the antagonizing activities of different Jun proteins in cell proliferation, with JunD being a negative regulator.
19. Thepot, D. et al. Targeted disruption of the murine junD gene results in multiple defects in male reproductive function. Development 127, 143-153 (2000).
20. Agarwal, S. K. et al. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 96, 143-152 (1999).
21. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57-70 (2000).
22. Liu, Y. et al. Inhibition of AP-1 transcription factor causes blockade of multiple signal transduction pathways and inhibits breast cancer growth. Oncogene 21, 7680-7689 (2002).
23. Park, Y. G., Nesterova, M., Agrawal, S. & Cho-Chung, Y. S. Dual blockade of cyclic AMP response element-(CRE) and AP-1-directed transcription by CRE-transcription factor decoy oligonucleotide. J. Biol. Chem. 274, 1573-1580 (1999).
24. Shaulian, E. & Karin, M. AP-1 in cell proliferation and survival. Oncogene 20, 2390-2400 (2001).
25. Schreiber, M. et al. Control of cell cycle progression by c-Jun is p53 dependent. Genes Dev. 13, 607-619 (1999).
26. Wisdom, R., Johnson, R. S. & Moore, C. c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms. EMBO J. 18, 188-197 (1999).
27. Behrens, A. et al. Impaired postnatal hepatocyte proliferation and liver regeneration in mice lacking c-jun in the liver. EMBO J. 21, 1782-1790 (2002).
28. Behrens, A., Sibilia, M. & Wagner, E. F. Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nature Genet. 21, 326-329 (1999). Shows that N-terminal phosphorylation of c-Jun by Jun amino-terminal kinases is not required during embryonic development, but is required for the stress response and for proliferation.
29. Bakiri, L., Lallemand, D., Bossy-Wetzel, E. & Yaniv, M. Cell cycle-dependent variations in c-Jun and JunB phosphorylation: a role in the control of cyclin D1 expression. EMBO J. 19, 2056-2068 (2000).
30. INK4a expression. EMBO J. 19, 2969-2979 (2000).
31. Weitzman, J. B., Fiette, L., Matsuo, K. & Yaniv, M. JunD protects cells from p53-dependent senescence and apoptosis. Mol. Cell 6, 1109-1119 (2000).
32. Shaulian, E. & Karin, M. AP-1 as a regulator of cell life and death. Nature Cell Biol. 4, E131-E136 (2002).
33. Zhang, J. et al. c-Fos regulates neuronal excitability and survival. Nature Genet, 30, 416-420 (2002).
34. Yang, D. D. et al. Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 389, 865-870 (1997).
35. Eferl, R. et al. Functions of c-Jun in liver and heart development. J. Cell Biol. 145, 1049-1061 (1999).
36. Whitfield, J., Neame, S. J., Paquet, L., Bernard, O. & Ham, J. Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and inhibiting mitochondrial cytochrome c release. Neuron 29, 629-643 (2001).
37. Kasibhatla, S. et al. DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-κB and AP-1. Mol. Cell 1, 543-551 (1998).
38. Rebollo, A. et al. Bcl-3 expression promotes cell survival following interleukin-4 deprivation and is controlled by AP1 and AP1-like transcription factors. Mol. Cell. Biol. 20, 3407-3416 (2000).
39. Lamb, J. A., Ventura, J. J., Hess, P., Flavell, R. A. & Davis, R. J. JunD mediates survival signaling by the JNK signal transduction pathway. Mol. Cell 11, 1479-1489 (2003).
40. Hu, E. et al. Targeted disruption of the c-fos gene demonstrates c-fos-dependent and -independent pathways for gene expression stimulated by growth factors or oncogenes. EMBO J. 13, 3094-3103 (1994).
41. Kustikova, O. et al. Fra-1 induces morphological transformation and increases in vitro invasiveness and motility of epithelioid adenocarcinoma cells. Mol. Cell. Biol. 18, 7095-7105 (1998).
42. Marconcini, L. et al. c-Fos-induced growth factor/vascular endothelial growth factor D induces angbgenesis in vivo and in vitro. Proc. Natl Acad. Sci. USA 96, 9671-9676 (1999).
43. Bossy-Wetzel, E., Bravo, R. & Hanahan, D. Transcription factors junB and c-jun are selectively up-regulated and functionally implicated in fibrosarcoma development. Genes Dev. 6, 2340-2351 (1992).
44. Toft, D. J., Rosenberg, S. B., Bergers, G., Volpert, O. & Linzer, D. I. Reactivation of proliferin gene expression is associated with increased angiogenesis in a cell culture model of fibrosarcoma tumor progression. Proc. Natl Acad. Sci. USA 98, 13055-13059 (2001).
45. Schorpp-Kistner, M., Wang, Z. O., Angel, P. & Wagner, E. F. JunB is essential for mammalian placentation. EMBO J. 18, 934-948 (1999).
46. Reichmann, E. et al. Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion. Cell 71, 1103-1116 (1992).
47. Fialka, I. et al. The estrogen-dependent c-JunER protein causes a reversible loss of mammary epithelial cell polarity involving a destabilization of adherens junctions. J. Cell Biol. 132, 1115-1132 (1996).
48. Saez, E. et al. c-Fos is required for malignant progression of skin tumors. Cell 82, 721-732 (1995). This study shows the requirement for c-Fos in skin-tumour progression.
49. Lamb, R. F. et al. AP-1-mediated invasion requires increased expression of the hyaluronan receptor CD44. Mol. Cell. Biol. 17, 963-976 (1997).
50. Bakid, L., Matsuo, K., Wisniewska, M., Wagner, E. F. & Yaniv, M. Promoter specificity and biological activity of tethered AP-1 dimers. Mol. Cell. Biol. 22, 4952-4964 (2002).
51. van Dam, H. & Castellazzi, M. Distinct roles of Jun: Fos and Jun:ATF dimers in oncogenesis. Oncogene 20, 2453-2464 (2001).
52. Chang, L. & Karin, M. Mammalian MAP kinase signalling cascades. Nature 410, 37-40 (2001).
53. Johnson, G. L. & Lapadat, R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298, 1911-1912 (2002).
54. Papachristou, D. J., Batistatou, A., Sykiotis, G. P., Varakis, I. & Papavassiliou, A. G. Activation of the JNK-AP-1 signal transduction pathway is associated with pathogenesis and progression of human osteosarcomas. Bone 32, 364-371 (2003).
55. Antonyak, M. A. et al. Bevated JNK activation contributes to the pathogenesis of human brain tumors. Oncogene 21, 5038-5046 (2002).
56. Kennedy, N. J. et al. Suppression of Ras-stimulated transformation by the JNK signal transduction pathway. Genes Dev. 17, 629637 (2003).
57. Lin, A. Activation of the JNK signaling pathway: breaking the brake on apoptosis. Bioessays 25, 17-24 (2003).
58. Behrens, A., Jochum, W., Sibilia, M. & Wagner, E. F. Oncogenic transformation by ras and fos is mediated by c-Jun N-terminal phosphorylation. Oncogene 19, 2657-2663 (2000).
59. Alani, R. et al. The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells. Mol. Cell. Biol. 11, 6286-6295 (1991).
60. Westwick, J. K. et al. Oncogenic Ras activates c-Jun via a separate pathway from the activation of extracellular signal-regulated kinases. Proc. Natl Acad. Sci. USA 91, 6030-6034 (1994).
61. Mechta, F., Lallemand, D., Pfarr, C. M. & Yaniv, M. Transformation by ras modifies AP1 composition and activity. Oncogene 14, 837-847 (1997).
62. Treinies, I., Paterson, H. F., Hooper, S., Wilson, R. & Marshall, C. J. Activated MEK stimulates expression of AP-1 components independently of phosphatidylinositol 3-kinase (PI3-kinase) but requires a PI3-kinase signal to stimulate DNA synthesis. Mol. Cell. Biol. 19, 321-329 (1999).
63. Johnson, R., Spiegelman, B., Hanahan, D. & Wisdom, R. Cellular transformation and malignancy induced by ras require c-jun. Mol. Cell. Biol. 16, 4504-4511 (1996).
64. Binetruy, B., Smeal, T. & Karin, M. Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. Nature 351, 122-127 (1991).
65. Smeal, T., Binetruy, B., Mercola, D. A., Birrer, M. & Karin, M. Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73. Nature 354, 494-496 (1991).
66. Sibilia, M. et al. The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development. Cell 102, 211-220 (2000).
67. Kallunki, T., Deng, T., Hibi, M. & Karin, M. c-Jun can recruit JNK to phosphorylate dimerization partners via specific docking interactions. Cell 87, 929-939 (1996).
68. Vandel, L. et al. Stepwise transformation of rat embryo fibroblasts: c-Jun, JunB, or JunD can cooperate with Ras for focus formation, but a c-Jun-containing heterodimer is required for immortalization. Mol. Cell. Biol. 16, 1881-1888 (1996).
69. Herrlich, P. Cross-talk between glucocorticoid receptor and AP-1. Oncogene 20, 2465-2475 (2001).
70. Altucci, L. & Gronemeyer, H. The promise of retinoids to fight against cancer. Nature Rev. Cancer 1, 181-193 (2001).
71. Mathas, S. et al. Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-κB. EMBO J. 21, 4104-4113 (2002). This study shows the importance of JUN proteins in human lymphoma pathogenesis and shows that c-JUN and JUNB mediate tumorigenesis by different molecular mechanisms.
72. Fleischmann, A. et al. Fra-1 replaces c-Fos-dependent functions in mice. Genes Dev. 14, 2695-2700 (2000).
73. Passegue, E., Jochum, W., Behrens, A., Ricci, R. & Wagner, E. F. JunB can substitute for Jun in mouse development and cell proliferation. Nature Genet. 30, 158-166 (2002).
74. Sprowles, A. & Wisdom, R. Oncogenic effect of delta deletion in v-Jun does not result from uncoupling Jun from JNK signaling. Oncogene 22, 498-506 (2003).
75. Glover, J. N. & Harrison, S. C. Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature 373, 257-261 (1995).
76. Bakin, A. V. & Curran, T. Role of DNA 5-methylcytosine transferase in cell transformation by fos. Science 283, 387-390 (1999).
77. Park, J. M. et al. AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells. Am. J. Physiol. 277, C294-C301 (1999).
78. Szabowski, A. et al. c-Jun and JunB antagonistically control cytokine-regulated mesenchymal-epidermal interaction in skin. Cell 103, 745-755 (2000).
79. Shaulian, E. et al. The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest. Cell 103, 897-907 (2000). This excellent study defines the role of c-Jun in the response to ultraviolet light. c-Jun is required for cell-cycle re-entry after ultraviolet irradiation by regulating Waf1 levels.
80. Ivanov, V. N. et al. Cooperation between STAT3 and c-jun suppresses Fas transcription. Mol. Cell 7, 517-528 (2001).
81. Hennigan, R. F., Hawker, K. L. & Ozanne, B. W. Fos-transformation activates genes associated with invasion. Oncogene 9, 3591-3600 (1994).
82. Spence, H. J. et al. Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells. Oncogene 19, 1266-1276 (2000).
83. Jooss, K. U. & Muller, R. Deregulation of genes encoding microfilament-associated proteins during Fos-induced morphological transformation. Oncogene 10, 603-608 (1995).