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AP-1 as a regulator of cell life and death

Nature Cell Biology volume 4, pages E131–E136 (2002)Cite this article

Abstract

The transcription factor AP-1 (activator protein-1) is involved in cellular proliferation, transformation and death. Using mice and cells lacking AP-1 components, the target-genes and molecular mechanisms mediating these processes were recently identified. Interestingly, the growth-promoting activity of c-Jun is mediated by repression of tumour suppressors, as well as upregulation of positive cell cycle regulators. Mostly, c-Jun is a positive regulator of cell proliferation, whereas JunB has the converse effect. The intricate relationships between the different Jun proteins, their activities and the mechanisms that mediate them will be discussed.

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Figure 1: A model describing the effects of AP-1 proteins on the major cell cycle regulators.
Figure 2: The effects of c-Jun in apoptosis.

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Article Open access 16 December 2023

Gian Luca Rampioni Vinciguerra, Marina Capece, … Carlo M. Croce

References

  1. Angel, P. & Karin, M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochem. Biophys. Acta 1072, 129–157 (1991).

    CAS  PubMed  Google Scholar 

  2. Chimenov, Y. & Kerppola, T. K. Close encounters of many kinds: Fos–Jun interactions that mediate transcription regulatory specificity. Oncogene 6, 533–542 (2001).

    Google Scholar 

  3. Ryseck, R. P. & Bravo, R. cJun, JunB, and JunD differ in their binding affinities to the AP-1 and CRE consensus sequences: effect of Fos proteins. Oncogene 6, 533–542 (1991).

    CAS  PubMed  Google Scholar 

  4. Schutte, J. et al. JunB inhibits and cFos stimulates the transforming and transactivating activities of cJun. Cell 59, 987–997 (1989).

    Article  CAS  PubMed  Google Scholar 

  5. Chiu, R., Angel, P. & Karin, M. JunB differs in its biological properties from, and is a negative regulator of c-Jun. Cell 59, 979–986 (1989).

    Article  CAS  PubMed  Google Scholar 

  6. Karin, M. The regulation of AP-1 activity by mitogen-activated protein kinases. J. Biol. Chem. 270, 16483–16486 (1995).

    Article  CAS  PubMed  Google Scholar 

  7. Karin, M., Liu, Z.-G. & Zandi, E. AP-1 function and regulation. Curr. Opin. Cell Biol. 9, 240–246 (1997).

    Article  CAS  PubMed  Google Scholar 

  8. Schreiber, M. et al. Control of cell cycle progression by c-Jun is p53 dependent. Genes Dev. 13, 607–619 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Passegue, E. & Wagner, E. F. JunB suppresses cell proliferation by transcriptional activation of p16(INK4a) expression. EMBO J. 19, 2969–2979 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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).

    Article  CAS  PubMed  Google Scholar 

  11. Pessah, M. et al. c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity. Proc. Natl Acad. Sci. USA 98, 6198–6120 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hsu, J. C., Cressman, D. E. & Taub, R. Promoter-specific trans-activation and inhibition mediated by JunB. Cancer Res. 53, 3789–3794 (1993).

    CAS  PubMed  Google Scholar 

  13. Chang, L. & Karin, M. Mammalian MAP kinase signalling cascades. Nature 410, 37–40 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Hill, C. S., Wynne, J. & Treisman, R. Serum-regulated transcription by serum response factor (Srf) – a novel role for the DNA binding domain. EMBO J. 13, 5421–5432 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gruda, M. C., Kovary, K., Metz, R. & Bravo, R. Regulation of Fra-1 and Fra-2 phosphorylation differs during the cell cycle of fibroblasts and phosphorylation in vitro by MAP kinase affects DNA binding activity. Oncogene 9, 2537–2547 (1994).

    CAS  PubMed  Google Scholar 

  16. Kato, Y. et al. BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J. 16, 7054–7066 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cavigelli, M., Dolfi, F., Claret, F. X. & Karin, M. Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation. EMBO J. 14, 5957–5964 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gupta, S., Campbell, D., Dérijard, B. & Davis, R. J. Transcription factor ATF2: regulation by the JNK signal transduction pathway. Science 267, 389–393 (1995).

    Article  CAS  PubMed  Google Scholar 

  19. Devary, Y., Gottlieb, R. A., Lau, L. & Karin, M. Rapid and preferential activation of the c-jun gene during the mammalian UV response. Mol. Cell. Biol. 11, 2804–2811 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Schonthal, A., Herrlich, P., Rahmsdorf, H. J. & Ponta, H. Requirement for fos gene expression in the transcriptional activation of collagenase by other oncogenes and phorbol esters. Cell 54, 325–334 (1988).

    Article  CAS  PubMed  Google Scholar 

  21. Hibi, M., Lin, A., Smeal, T., Minden, A. & Karin, M. Identification of an oncoprotein-responsive and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 7, 2135–2148 (1993).

    Article  CAS  PubMed  Google Scholar 

  22. Dérijard, B. et al. JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76, 1025–1037 (1994).

    Article  PubMed  Google Scholar 

  23. Han, J., Jiang, Y., Li, Z., Kravchenko, V. V. & Ulevitch, R. J. Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation. Nature 386, 296–299 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Shaulian, E. & Karin, M. AP-1 in cell proliferation and survival. Oncogene 20, 2390–2400 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Kovary, K. & Bravo, R. The jun and fos protein families are both required for cell cycle progression in fibroblasts. Mol. Cell. Biol. 11, 4466–4472 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Brown, J. R. et al. Fos family members induce cell cycle entry by activating cyclin D1. Mol. Cell Biol. 18, 5609–5619 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Brusselbach, S. et al. Cell proliferation and cell cycle progression are not impaired in fibroblasts and ES cells lacking c-Fos. Oncogene 10, 79–86 (1995).

    CAS  PubMed  Google Scholar 

  28. Thepot, D. et al. Targeted disruption of the murine junD gene results in multiple defects in male reproductive function. Development 127, 143–153 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. 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).

    Article  CAS  PubMed  Google Scholar 

  30. Johnson, R. S., van Lingen, B., Papaioannou, V. E. & Spiegelman, B. W. A null mutation at the c-jun locus causes embryonic lethality and retarded cell growth in culture. Genes Dev. 7, 1309–1317 (1993).

    Article  CAS  PubMed  Google Scholar 

  31. Eferl, R. et al. Functions of c-jun in liver and heart development. J. Cell Biol. 145, 1049–1061 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Szabowski, A. et al. c-Jun and JunB antagonistically control cytokine-regulated mesenchymal–epidermal interaction in skin. Cell 103, 745–755 (2000).

    Article  CAS  PubMed  Google Scholar 

  33. Wisdom, R., Johnson, R. S. & Moore, C. c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms. EMBO J. 18, 188–197 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xiong, Y. et al. p21 is a universal inhibitor of cyclin kinases. Nature 366, 701–704 (1993).

    Article  CAS  PubMed  Google Scholar 

  35. El-Deiry, W. S. et al. WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817–825 (1993).

    Article  CAS  PubMed  Google Scholar 

  36. Clark, W. et al. v-Jun overrides the mitogen dependence of S-phase entry by deregulating retinoblastoma protein phosphorylation and E2F-pocket protein interactions as a consequence of enhanced cyclin E–cdk2 catalytic activity. Mol. Cell Biol. 20, 2529–2542 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hennigan, R. F. & Stambrook, P. J. Dominant negative c-jun inhibits activation of the cyclin D1 and cyclin E kinase complexes. Mol. Biol. Cell 12, 2352–2363 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Schutte, J., Minna, J. D. & Birrer, M. Deregulated expression of human {Ic-jun} transforms primary rat embryo cells in cooperation with and activated c-Ha-{Iras} gene and transforms Rat-la cells as a single gene. Proc. Natl Acad. Sci. USA 86, 2257–2261 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schorpp-Kistner, M., Wang, Z. Q., Angel, P. & Wagner, E. F. JunB is essential for mammalian placentation. EMBO J. 18, 934–948 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 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).

    Article  CAS  PubMed  Google Scholar 

  42. Passegue, E., Jochum, W., Behrens, A., Ricci, R. & Wagner, E. JunB can substitute for c-Jun in mouse development and cell proliferation. Nature Genet. 30, 158–166 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Weitzman, J. B., Fiette, L., Matsuo, K. & Yaniv, M. JunD protects cells from p53-dependent senescence and apoptosis. Mol. Cell 6, 1109–1119 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Sherr, C. J. Tumor surveillance via the ARF-p53 pathway. Genes Dev. 12, 2984–2991 (1998).

    Article  CAS  PubMed  Google Scholar 

  45. Agarwal, S. K. et al. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 96, 143–152 (1999).

    Article  CAS  PubMed  Google Scholar 

  46. Pfarr, C. M. et al. Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell 76, 747–760 (1994).

    Article  CAS  PubMed  Google Scholar 

  47. Maki, Y., Bos, T. J., Davis, C., Starbuck, M. & Vogt, P. K. Avian sarcoma cirus 17 carries the Jun oncogene. Proc. Natl Acad. Sci. USA 84, 2848–2852 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. van Straaten, F., Muller, R., Curran, T., Van Beveren, C. & Verma, I. M. 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, 3183–3187 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. 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).

    Article  CAS  PubMed  Google Scholar 

  52. Hartl, M., Reiter, F., Bader, A. G., Castellazzi, M. & Bister, K. JAC, a direct target of oncogenic transcription factor Jun, is involved in cell transformation and tumorigenesis. Proc. Natl Acad. Sci. USA 98, 13601–13606 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fu, S., Bottoli, I., Goller, M. & Vogt, P. K. Heparin-binding epidermal growth factor-like growth factor, a v-Jun target gene, induces oncogenic transformation. Proc. Natl Acad. Sci. USA 96, 5716–5721 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Miller, A., Curran, T. & Verma, I. cFos can induce cellular transformation: novel mechanism of activating a cellular oncogene. Cell 36, 51–60 (1984).

    Article  CAS  PubMed  Google Scholar 

  55. Mechta, F., Lallemand, D., Pfarr, C. M. & Yaniv, M. Transformation by ras modifies AP1 composition and activity. Oncogene 14, 837–847 (1997).

    Article  CAS  PubMed  Google Scholar 

  56. Bakin, A. V. & Curran, T. Role of DNA 5-methylcytosine transferase in cell transformation by fos. Science 283, 387–390 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. van Dam, H. et al. Autocrine growth and anchorage independence: two complementing Jun-controlled genetic programs of cellular transformation. Genes Dev. 12, 1227–1239 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ruther, U., Garber, C., Komitowski, D., Muller, R. & Wagner, E. F. Deregulated c-fos expression interferes with normal bone development in transgenic mice. Nature 325, 412–416 (1987).

    Article  CAS  PubMed  Google Scholar 

  60. Ruther, U., Komitowski, D., Schubert, F. R. & Wagner, E. F. c-fos expression induces bone tumors in transgenic mice. Oncogene 4, 861–865 (1989).

    CAS  PubMed  Google Scholar 

  61. Saez, E. et al. c-fos is required for malignant progression of skin tumors. Cell 82, 721–732 (1999).

    Article  Google Scholar 

  62. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Jochum, W., Passegue, E. & Wagner, E. F. AP-1 in mouse development and tumorigenesis. Oncogene 20, 2401–2412 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. Wulf, G. M. et al. EMBO J. 20, 3459–3472 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Smeyne, R. Continuous c-Fos expression procedes programmed cell death in vivo. Nature 363, 166–169 (1993).

    Article  CAS  PubMed  Google Scholar 

  66. Marti, A. et al. Protein kinase A and AP-1 (c-Fos/JunD) are induced during apoptosis of mouse mammary epithelial cells. Oncogene 9, 1213–1223 (1994).

    CAS  PubMed  Google Scholar 

  67. Buttyan, R., Zakeri, Z., Lockshin, R. & Wolgemuth, D. Cascade induction of c-fos, c-myc, and heat shock 70K transcripts during regression of the rat ventral prostate gland. Mol. Endocrinol. 2, 650–657 (1988).

    Article  CAS  PubMed  Google Scholar 

  68. Estus, S., et al. Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis. J. Cell Biol. 127, 1717–1727 (1994).

    Article  CAS  PubMed  Google Scholar 

  69. Ham, J. et al. A c-Jun dominant negative mutant protects sympathetic neurons against programmed cell death. Neuron 14, 927–939 (1995).

    Article  CAS  PubMed  Google Scholar 

  70. Colotta, F., Polentarutti, N., Sironi, M. & Mantovani, A. Expression and involvement of c-fos and c-jun protooncogenes in programmed cell death induced by growth factor deprivation in lymphoid cell lines. J. Biol. Chem. 267, 18278–18283 (1992).

    Article  CAS  PubMed  Google Scholar 

  71. Karin, M. Mitogen-activated protein kinase cascades as regulators of stress responses. Ann. NY Acad. Sci. 851, 139–146 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Bossy-Wetzel, E., Bakiri, L. & Yaniv, M. Induction of apoptosis by the transcription factor c-Jun. EMBO J. 16, 1695–1709 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Preston, G. A. et al. Induction of apoptosis by c-Fos protein. Mol. Cell Biol. 16, 211–218 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Le-Niculescu, H. et al. Withdrawal of survival factors results in activation of the JNK pathway in neuronal cells leading to Fas ligand induction and cell death. Mol. Cell. Biol. 19, 751–763 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J. & Greenberg, M. E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270, 1326–1331 (1995).

    Article  CAS  PubMed  Google Scholar 

  76. J., W., 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).

    Article  Google Scholar 

  77. Hafezi, F. et al. The absence of c-fos prevents light-induced apoptotic cell death of photoreceptors in retinal degeneration in vivo. Nature Med. 3, 346–349 (1997).

    Article  CAS  PubMed  Google Scholar 

  78. 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).

    Article  CAS  PubMed  Google Scholar 

  79. Yang, D. et al. Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 389, 865–870 (1997).

    Article  CAS  PubMed  Google Scholar 

  80. De Smaele, E. et al. Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling. Nature 414, 308–313 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. Tang, G. et al. Inhibition of JNK activation through NF-κB target genes. Nature 414, 313–317 (2001).

    Article  CAS  PubMed  Google Scholar 

  82. Xu, X., Raber, J., Yang, D., Su, B. & Mucke, L. Dynamic regulation of c-Jun N-terminal kinase activity in mouse brain by environmental stimuli. Proc. Natl Acad. Sci. USA 94, 12655–12660 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kenney, A. M. & Kocsis, J. D. Peripheral axotomy induces long-term c-Jun amino-terminal kinase-1 activation and activator protein-1 binding activity by c-Jun and junD in adult rat dorsal root ganglia in vivo. J. Neurosci. 18, 1318–1328 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Herdegen, T. et al. Lasting N-terminal phosphorylation of c-Jun and activation of c-Jun N-terminal kinases after neuronal injury. J. Neurosci. 18, 5124–5135 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Tournier, C. et al. Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science 288, 870–874 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Kolbus, A. et al. c-Jun-dependent CD95-L expression is a rate-limiting step in the induction of apoptosis by alkylating agents. Mol. Cell. Biol. 20, 575–582 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Verheij, M. et al. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380, 75–79 (1996).

    Article  CAS  PubMed  Google Scholar 

  88. Ivanov, V. N. et al. Cooperation between STAT3 and c-jun suppresses Fas transcription. Mol. Cell 7, 517–528 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Owen-Schaub, L. B. et al. Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol. Cell. Biol. 15, 3032–3049 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Smith, M. L. & Fornace, A. J. Jr. p53-mediated protective responses to UV irradiation. Proc. Natl Acad. Sci. USA 94, 12255–12257 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Bissonnette, N. & Hunting, D. J. p21-induced cycle arrest in G(1) protects cells from apoptosis induced by UV-irradiation or RNA polymerase II blockage. Oncogene 16, 3461–3469 (1998).

    Article  CAS  PubMed  Google Scholar 

  92. Gniadecki, R., Hansen, M. & Wulf, H. C. Resistance of senescent keratinocytes to UV-induced apoptosis. Cell. Mol. Biol. 46, 121–127 (2000).

    CAS  PubMed  Google Scholar 

  93. Hilberg, F., Aguzzi, A., Howells, N. & Wagner, E. F. c-jun is essential for normal mouse development and hepatogenesis. Nature 365, 179–181 (1993).

    Article  CAS  PubMed  Google Scholar 

  94. Kuan, C. Y. et al. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron 22, 667–676 (1999).

    Article  CAS  PubMed  Google Scholar 

  95. Liu, Z.-G., Hu, H., Goeddel, D. V. & Karin, M. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis, while NF-κB activation prevents cell death. Cell 87, 565–576 (1996).

    Article  CAS  PubMed  Google Scholar 

  96. Natoli, G. et al. Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway. Science 275, 200–203 (1997).

    Article  CAS  PubMed  Google Scholar 

  97. Nishina, H. et al. Stress-signaling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3. Nature 385, 350–353 (1997).

    Article  CAS  PubMed  Google Scholar 

  98. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Experimental Medicine and Cancer Research, School of Medicine, the Hebrew University, Jerusalem, 91120, Israel

    Eitan Shaulian

  2. Department of Pharmacology, Laboratory of Gene Regulation and Signal Transduction, University of California San Diego, La Jolla, 92093, CA, USA

    Michael Karin

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Shaulian, E., Karin, M. AP-1 as a regulator of cell life and death. Nat Cell Biol 4, E131–E136 (2002). https://doi.org/10.1038/ncb0502-e131

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