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Apoptosis

, Volume 14, Issue 8, pp 1021–1028 | Cite as

Correcting developmental errors by apoptosis: lessons from Drosophila JNK signaling

  • Tatsushi IgakiEmail author
Apoptosis in Drosophila

Abstract

Spatio-temporal regulation of the cell death machinery is essential for normal development and homeostasis of multicellular organisms. While the molecular basis for the central cell death machinery driven by caspases is now well documented, its regulatory mechanisms, especially in the context of living animals, remain to be clarified. The c-Jun N-terminal kinase (JNK) pathway is an evolutionarily conserved kinase cascade that regulates the apoptotic machinery. In mammals, JNK signaling has been implicated in stress-induced apoptosis. Drosophila genetics has now provided evidence of a novel role for JNK-mediated cell death signaling in eliminating developmentally aberrant cells from a tissue. The JNK-dependent cell-elimination system is orchestrated by cell-cell communication between normal and aberrant cells and is essential for ensuring developmental robustness, as well as for protecting organisms against fatal abnormalities such as neoplastic development. These processes are mediated by cell competition, morphogenetic apoptosis, and intrinsic tumor suppression. A combinatorial approach using both genetic and live-imaging systems in Drosophila will be extremely powerful to decipher how JNK-mediated apoptosis works within multicellular communities.

Keywords

Apoptosis Cell death JNK Drosophila Intrinsic tumor suppression Cell competition Morphogenetic apoptosis 

Notes

Acknowledgments

I would like to thank Shizue Ohsawa and Jose Carlos Pastor-Pareja for thoughtful discussions and valuable comments on the manuscript, Masayuki Miura for encouragement, and anonymous reviewers for helpful comments. Work in my laboratory is supported by grants from the Japanese Ministry of Education, Science, Sports, Culture and Technology, the Japan Society for the Promotion of Science, the G-COE program for Global Center for Education and Research in Integrative Membrane Biology, the Sumitomo Foundation, the Astellas Foundation for Research on Metabolic Disorders, the Novartis Foundation for the Promotion of Science, and the Human Frontier Science Program.

References

  1. 1.
    Schaeffer HJ, Weber MJ (1999) Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 19:2435–2444PubMedGoogle Scholar
  2. 2.
    Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410:37–40. doi: 10.1038/35065000 PubMedCrossRefGoogle Scholar
  3. 3.
    Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103:239–252. doi: 10.1016/S0092-8674(00)00116-1 PubMedCrossRefGoogle Scholar
  4. 4.
    Weston CR, Davis RJ (2002) The JNK signal transduction pathway. Curr Opin Genet Dev 12:14–21. doi: 10.1016/S0959-437X(01)00258-1 PubMedCrossRefGoogle Scholar
  5. 5.
    Riesgo-Escovar JR, Jenni M, Fritz A, Hafen E (1996) The Drosophila Jun-N-terminal kinase is required for cell morphogenesis but not for DJun-dependent cell fate specification in the eye. Genes Dev 10:2759–2768. doi: 10.1101/gad.10.21.2759 PubMedCrossRefGoogle Scholar
  6. 6.
    Sluss HK, Han Z, Barrett T et al (1996) A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila. Genes Dev 10:2745–2758. doi: 10.1101/gad.10.21.2745 PubMedCrossRefGoogle Scholar
  7. 7.
    Glise B, Bourbon H, Noselli S (1995) Hemipterous encodes a novel Drosophila MAP kinase kinase, required for epithelial cell sheet movement. Cell 83:451–461. doi: 10.1016/0092-8674(95)90123-X PubMedCrossRefGoogle Scholar
  8. 8.
    Boutros M, Agaisse H, Perrimon N (2002) Sequential activation of signaling pathways during innate immune responses in Drosophila. Dev Cell 3:711–722. doi: 10.1016/S1534-5807(02)00325-8 PubMedCrossRefGoogle Scholar
  9. 9.
    Silverman N, Zhou R, Erlich RL et al (2003) Immune activation of NF-kappaB and JNK requires Drosophila TAK1. J Biol Chem 278:48928–48934. doi: 10.1074/jbc.M304802200 PubMedCrossRefGoogle Scholar
  10. 10.
    Takatsu Y, Nakamura M, Stapleton M et al (2000) TAK1 participates in c-Jun N-terminal kinase signaling during Drosophila development. Mol Cell Biol 20:3015–3026. doi: 10.1128/MCB.20.9.3015-3026.2000 PubMedCrossRefGoogle Scholar
  11. 11.
    Chen W, White MA, Cobb MH (2002) Stimulus-specific requirements for MAP3 kinases in activating the JNK pathway. J Biol Chem 277:49105–49110. doi: 10.1074/jbc.M204934200 PubMedCrossRefGoogle Scholar
  12. 12.
    Kuranaga E, Kanuka H, Igaki T et al (2002) Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila. Nat Cell Biol 4:705–710. doi: 10.1038/ncb842 PubMedCrossRefGoogle Scholar
  13. 13.
    Sathyanarayana P, Barthwal MK, Lane ME et al (2003) Drosophila mixed lineage kinase/slipper, a missing biochemical link in Drosophila JNK signaling. Biochim Biophys Acta 1640:77–84. doi: 10.1016/S0167-4889(03)00022-3 PubMedCrossRefGoogle Scholar
  14. 14.
    Stronach B, Perrimon N (2002) Activation of the JNK pathway during dorsal closure in Drosophila requires the mixed lineage kinase, slipper. Genes Dev 16:377–387. doi: 10.1101/gad.953002 PubMedCrossRefGoogle Scholar
  15. 15.
    Inoue H, Tateno M, Fujimura-Kamada K et al (2001) A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK. EMBO J 20:5421–5430. doi: 10.1093/emboj/20.19.5421 PubMedCrossRefGoogle Scholar
  16. 16.
    Teramoto H, Coso OA, Miyata H, Igishi T, Miki T, Gutkind JS (1996) Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase/stress-activated protein kinase pathway. A role for mixed lineage kinase 3/protein-tyrosine kinase 1, a novel member of the mixed lineage kinase family. J Biol Chem 271:27225–27228. doi: 10.1074/jbc.271.8.3963 Google Scholar
  17. 17.
    Su YC, Treisman JE, Skolnik EY (1998) The Drosophila Ste20-related kinase misshapen is required for embryonic dorsal closure and acts through a JNK MAPK module on an evolutionarily conserved signaling pathway. Genes Dev 12:2371–2380. doi: 10.1101/gad.12.15.2371 PubMedCrossRefGoogle Scholar
  18. 18.
    Cha GH, Cho KS, Lee JH et al (2003) Discrete functions of TRAF1 and TRAF2 in Drosophila melanogaster mediated by c-Jun N-terminal kinase and NF-kappaB-dependent signaling pathways. Mol Cell Biol 23:7982–7991. doi: 10.1128/MCB.23.22.7982-7991.2003 PubMedCrossRefGoogle Scholar
  19. 19.
    Liu H, Su YC, Becker E, Treisman J, Skolnik EY (1999) A Drosophila TNF-receptor-associated factor (TRAF) binds the ste20 kinase Misshapen and activates Jun kinase. Curr Biol 9:101–104. doi: 10.1016/S0960-9822(99)80023-2 PubMedCrossRefGoogle Scholar
  20. 20.
    Xue L, Igaki T, Kuranaga E, Kanda H, Miura M, Xu T (2007) Tumor suppressor CYLD regulates JNK-induced cell death in Drosophila. Dev Cell 13:446–454. doi: 10.1016/j.devcel.2007.07.012 PubMedCrossRefGoogle Scholar
  21. 21.
    Igaki T, Kanda H, Yamamoto-Goto Y et al (2002) Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. EMBO J 21:3009–3018. doi: 10.1093/emboj/cdf306 PubMedCrossRefGoogle Scholar
  22. 22.
    Kanda H, Miura M (2004) Regulatory roles of JNK in programmed cell death. J Biochem 136:1–6. doi: 10.1093/jb/mvh098 PubMedCrossRefGoogle Scholar
  23. 23.
    Kauppila S, Maaty WS, Chen P et al (2003) Eiger and its receptor, Wengen, comprise a TNF-like system in Drosophila. Oncogene 22:4860–4867. doi: 10.1038/sj.onc.1206715 PubMedCrossRefGoogle Scholar
  24. 24.
    Moreno E, Yan M, Basler K (2002) Evolution of TNF signaling mechanisms: JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily. Curr Biol 12:1263–1268. doi: 10.1016/S0960-9822(02)00954-5 PubMedCrossRefGoogle Scholar
  25. 25.
    Ishimaru S, Ueda R, Hinohara Y, Ohtani M, Hanafusa H (2004) PVR plays a critical role via JNK activation in thorax closure during Drosophila metamorphosis. EMBO J 23:3984–3994. doi: 10.1038/sj.emboj.7600417 PubMedCrossRefGoogle Scholar
  26. 26.
    Boutros M, Paricio N, Strutt DI, Mlodzik M (1998) Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Cell 94:109–118. doi: 10.1016/S0092-8674(00)81226-X PubMedCrossRefGoogle Scholar
  27. 27.
    Zeitlinger J, Kockel L, Peverali FA, Jackson DB, Mlodzik M, Bohmann D (1997) Defective dorsal closure and loss of epidermal decapentaplegic expression in Drosophila fos mutants. EMBO J 16:7393–7401. doi: 10.1093/emboj/16.24.7393 PubMedCrossRefGoogle Scholar
  28. 28.
    Martin-Blanco E, Gampel A, Ring J et al (1998) Puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. Genes Dev 12:557–570. doi: 10.1101/gad.12.4.557 PubMedCrossRefGoogle Scholar
  29. 29.
    Jacinto A, Woolner S, Martin P (2002) Dynamic analysis of dorsal closure in Drosophila: from genetics to cell biology. Dev Cell 3:9–19. doi: 10.1016/S1534-5807(02)00208-3 PubMedCrossRefGoogle Scholar
  30. 30.
    Noselli S, Agnes F (1999) Roles of the JNK signaling pathway in Drosophila morphogenesis. Curr Opin Genet Dev 9:466–472. doi: 10.1016/S0959-437X(99)80071-9 PubMedCrossRefGoogle Scholar
  31. 31.
    Xia Y, Karin M (2004) The control of cell motility and epithelial morphogenesis by Jun kinases. Trends Cell Biol 14:94–101. doi: 10.1016/j.tcb.2003.12.005 PubMedCrossRefGoogle Scholar
  32. 32.
    Zeitlinger J, Bohmann D (1999) Thorax closure in Drosophila: involvement of Fos and the JNK pathway. Development 126:3947–3956PubMedGoogle Scholar
  33. 33.
    Pastor-Pareja JC, Grawe F, Martin-Blanco E, Garcia-Bellido A (2004) Invasive cell behavior during Drosophila imaginal disc eversion is mediated by the JNK signaling cascade. Dev Cell 7:387–399. doi: 10.1016/j.devcel.2004.07.022 PubMedCrossRefGoogle Scholar
  34. 34.
    Galko MJ, Krasnow MA (2004) Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biol 2:E239. doi: 10.1371/journal.pbio.0020239 PubMedCrossRefGoogle Scholar
  35. 35.
    Martin P, Parkhurst SM (2004) Parallels between tissue repair and embryo morphogenesis. Development 131:3021–3034. doi: 10.1242/dev.01253 PubMedCrossRefGoogle Scholar
  36. 36.
    Ramet M, Manfruelli P, Pearson A, Mathey-Prevot B, Ezekowitz RA (2002) Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature 416:644–648. doi: 10.1038/nature735 CrossRefGoogle Scholar
  37. 37.
    Delaney JR, Stoven S, Uvell H, Anderson KV, Engstrom Y, Mlodzik M (2006) Cooperative control of Drosophila immune responses by the JNK and NF-kappaB signaling pathways. EMBO J 25:3068–3077. doi: 10.1038/sj.emboj.7601182 PubMedCrossRefGoogle Scholar
  38. 38.
    Pastor-Pareja JC, Wu M, Xu T (2008) An innate immune response of blood cells to tumors and tissue damage in Drosophila. Dis Model Mech 1:144–154. doi: 10.1242/dmm.000950 PubMedCrossRefGoogle Scholar
  39. 39.
    Paricio N, Feiguin F, Boutros M, Eaton S, Mlodzik M (1999) The Drosophila STE20-like kinase misshapen is required downstream of the Frizzled receptor in planar polarity signaling. EMBO J 18:4669–4678. doi: 10.1093/emboj/18.17.4669 PubMedCrossRefGoogle Scholar
  40. 40.
    Weber U, Paricio N, Mlodzik M (2000) Jun mediates Frizzled-induced R3/R4 cell fate distinction and planar polarity determination in the Drosophila eye. Development 127:3619–3629PubMedGoogle Scholar
  41. 41.
    Sanyal S, Basole A, Krishnan KS (1999) Phenotypic interaction between temperature-sensitive paralytic mutants comatose and paralytic suggests a role for N-ethylmaleimide-sensitive fusion factor in synaptic vesicle cycling in Drosophila. J Neurosci 19:RC47Google Scholar
  42. 42.
    Wang MC, Bohmann D, Jasper H (2003) JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila. Dev Cell 5:811–816. doi: 10.1016/S1534-5807(03)00323-X PubMedCrossRefGoogle Scholar
  43. 43.
    Wang MC, Bohmann D, Jasper H (2005) JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell 121:115–125. doi: 10.1016/j.cell.2005.02.030 PubMedCrossRefGoogle Scholar
  44. 44.
    Biteau B, Hochmuth CE, Jasper H (2008) JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3:442–455. doi: 10.1016/j.stem.2008.07.024 PubMedCrossRefGoogle Scholar
  45. 45.
    Igaki T, Pagliarini RA, Xu T (2006) Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr Biol 16:1139–1146. doi: 10.1016/j.cub.2006.04.042 PubMedCrossRefGoogle Scholar
  46. 46.
    Srivastava A, Pastor-Pareja JC, Igaki T, Pagliarini R, Xu T (2007) Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion. Proc Natl Acad Sci USA 104:2721–2726. doi: 10.1073/pnas.0611666104 PubMedCrossRefGoogle Scholar
  47. 47.
    Uhlirova M, Bohmann D (2006) JNK- and Fos-regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila. EMBO J 25:5294–5304. doi: 10.1038/sj.emboj.7601401 PubMedCrossRefGoogle Scholar
  48. 48.
    Adachi-Yamada T, O’Connor MB (2004) Mechanisms for removal of developmentally abnormal cells: cell competition and morphogenetic apoptosis. J Biochem 136:13–17. doi: 10.1093/jb/mvh099 PubMedCrossRefGoogle Scholar
  49. 49.
    Kuranaga E, Miura M (2002) Molecular genetic control of caspases and JNK-mediated neural cell death. Arch Histol Cytol 65:291–300. doi: 10.1679/aohc.65.291 PubMedCrossRefGoogle Scholar
  50. 50.
    Moreno E (2008) Is cell competition relevant to cancer? Nat Rev Cancer 8:141–147. doi: 10.1038/nrc2252 PubMedCrossRefGoogle Scholar
  51. 51.
    Stronach B (2005) Dissecting JNK signaling, one KKKinase at a time. Dev Dyn 232:575–584. doi: 10.1002/dvdy.20283 PubMedCrossRefGoogle Scholar
  52. 52.
    Dhanasekaran DN, Reddy EP (2008) JNK signaling in apoptosis. Oncogene 27:6245–6251. doi: 10.1038/onc.2008.301 PubMedCrossRefGoogle Scholar
  53. 53.
    Chen P, Nordstrom W, Gish B, Abrams JM (1996) Grim, a novel cell death gene in Drosophila. Genes Dev 10:1773–1782. doi: 10.1101/gad.10.14.1773 PubMedCrossRefGoogle Scholar
  54. 54.
    Grether ME, Abrams JM, Agapite J, White K, Steller H (1995) The head involution defective gene of Drosophila melanogaster functions in programmed cell death. Genes Dev 9:1694–1708. doi: 10.1101/gad.9.14.1694 PubMedCrossRefGoogle Scholar
  55. 55.
    White K, Grether ME, Abrams JM, Young L, Farrell K, Steller H (1994) Genetic control of programmed cell death in Drosophila. Science 264:677–683. doi: 10.1126/science.8171319 PubMedCrossRefGoogle Scholar
  56. 56.
    Martin SJ (2002) Destabilizing influences in apoptosis: sowing the seeds of IAP destruction. Cell 109:793–796. doi: 10.1016/S0092-8674(02)00802-4 PubMedCrossRefGoogle Scholar
  57. 57.
    McEwen DG, Peifer M (2005) Puckered, a Drosophila MAPK phosphatase, ensures cell viability by antagonizing JNK-induced apoptosis. Development 132:3935–3946. doi: 10.1242/dev.01949 PubMedCrossRefGoogle Scholar
  58. 58.
    Luo X, Puig O, Hyun J, Bohmann D, Jasper H (2007) Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation. EMBO J 26:380–390. doi: 10.1038/sj.emboj.7601484 PubMedCrossRefGoogle Scholar
  59. 59.
    Lee JH, Koh H, Kim M et al (2006) JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila. Cell Death Differ 13:1110–1122. doi: 10.1038/sj.cdd.4401790 PubMedCrossRefGoogle Scholar
  60. 60.
    Griswold AJ, Chang KT, Runko AP, Knight MA, Min KT (2008) Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila. Proc Natl Acad Sci USA 105:8673–8678. doi: 10.1073/pnas.0803837105 PubMedCrossRefGoogle Scholar
  61. 61.
    Kanda H, Igaki T, Kanuka H, Yagi T, Miura M (2002) Wengen, a member of the Drosophila tumor necrosis factor receptor superfamily, is required for Eiger signaling. J Biol Chem 277:28372–28375. doi: 10.1074/jbc.C200324200 PubMedCrossRefGoogle Scholar
  62. 62.
    Geuking P, Narasimamurthy R, Basler K (2005) A genetic screen targeting the tumor necrosis factor/Eiger signaling pathway: identification of Drosophila TAB 2 as a functionally conserved component. Genetics 171:1683–1694. doi: 10.1534/genetics.105.045534 PubMedCrossRefGoogle Scholar
  63. 63.
    Brandt SM, Dionne MS, Khush RS, Pham LN, Vigdal TJ, Schneider DS (2004) Secreted bacterial effectors and host-produced Eiger/TNF drive death in a Salmonella-infected fruit fly. PLoS Biol 2:e418. doi: 10.1371/journal.pbio.0020418 PubMedCrossRefGoogle Scholar
  64. 64.
    Schneider DS, Ayres JS, Brandt SM et al (2007) Drosophila eiger mutants are sensitive to extracellular pathogens. PLoS Pathog 3:e41. doi: 10.1371/journal.ppat.0030041 PubMedCrossRefGoogle Scholar
  65. 65.
    Bidla G, Dushay MS, Theopold U (2007) Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger. J Cell Sci 120:1209–1215. doi: 10.1242/jcs.03420 PubMedCrossRefGoogle Scholar
  66. 66.
    Wang H, Cai Y, Chia W, Yang X (2006) Drosophila homologs of mammalian TNF/TNFR-related molecules regulate segregation of Miranda/Prospero in neuroblasts. EMBO J 25:5783–5793. doi: 10.1038/sj.emboj.7601461 PubMedCrossRefGoogle Scholar
  67. 67.
    Kato K, Awasaki T, Ito K (2009) Neuronal programmed cell death induces glial cell division in the adult Drosophila brain. Development 136:51–59. doi: 10.1242/dev.023366 PubMedCrossRefGoogle Scholar
  68. 68.
    Brodsky MH, Weinert BT, Tsang G et al (2004) Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage. Mol Cell Biol 24:1219–1231. doi: 10.1128/MCB.24.3.1219-1231.2004 PubMedCrossRefGoogle Scholar
  69. 69.
    Adachi-Yamada T, Fujimura-Kamada K, Nishida Y, Matsumoto K (1999) Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing. Nature 400:166–169. doi: 10.1038/22112 PubMedCrossRefGoogle Scholar
  70. 70.
    Gibson MC, Perrimon N (2005) Extrusion and death of DPP/BMP-compromised epithelial cells in the developing Drosophila wing. Science 307:1785–1789. doi: 10.1126/science.1104751 PubMedCrossRefGoogle Scholar
  71. 71.
    Shen J, Dahmann C (2005) Extrusion of cells with inappropriate Dpp signaling from Drosophila wing disc epithelia. Science 307:1789–1790. doi: 10.1126/science.1104784 PubMedCrossRefGoogle Scholar
  72. 72.
    Adachi-Yamada T, O’Connor MB (2002) Morphogenetic apoptosis: a mechanism for correcting discontinuities in morphogen gradients. Dev Biol 251:74–90. doi: 10.1006/dbio.2002.0821 PubMedCrossRefGoogle Scholar
  73. 73.
    Manjon C, Sanchez-Herrero E, Suzanne M (2007) Sharp boundaries of Dpp signalling trigger local cell death required for Drosophila leg morphogenesis. Nat Cell Biol 9:57–63. doi: 10.1038/ncb1518 PubMedCrossRefGoogle Scholar
  74. 74.
    Morata G, Ripoll P (1975) Minutes: mutants of drosophila autonomously affecting cell division rate. Dev Biol 42:211–221. doi: 10.1016/0012-1606(75)90330-9 PubMedCrossRefGoogle Scholar
  75. 75.
    Moreno E, Basler K, Morata G (2002) Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416:755–759. doi: 10.1038/416755a PubMedCrossRefGoogle Scholar
  76. 76.
    Moreno E, Basler K (2004) dMyc transforms cells into super-competitors. Cell 117:117–129. doi: 10.1016/S0092-8674(04)00262-4 PubMedCrossRefGoogle Scholar
  77. 77.
    de la Cova C, Abril M, Bellosta P, Gallant P, Johnston LA (2004) Drosophila myc regulates organ size by inducing cell competition. Cell 117:107–116. doi: 10.1016/S0092-8674(04)00214-4 CrossRefGoogle Scholar
  78. 78.
    Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1:46–54. doi: 10.1038/35094059 PubMedCrossRefGoogle Scholar
  79. 79.
    Fish EM, Molitoris BA (1994) Alterations in epithelial polarity and the pathogenesis of disease states. N Engl J Med 330:1580–1588. doi: 10.1056/NEJM199406023302207 PubMedCrossRefGoogle Scholar
  80. 80.
    Lowe SW, Cepero E, Evan G (2004) Intrinsic tumour suppression. Nature 432:307–315. doi: 10.1038/nature03098 PubMedCrossRefGoogle Scholar
  81. 81.
    Brumby AM, Richardson HE (2003) scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J 22:5769–5779. doi: 10.1093/emboj/cdg548 PubMedCrossRefGoogle Scholar
  82. 82.
    Uhlirova M, Jasper H, Bohmann D (2005) Non-cell-autonomous induction of tissue overgrowth by JNK/Ras cooperation in a Drosophila tumor model. Proc Natl Acad Sci USA 102:13123–13128. doi: 10.1073/pnas.0504170102 PubMedCrossRefGoogle Scholar
  83. 83.
    Herz HM, Chen Z, Scherr H, Lackey M, Bolduc C, Bergmann A (2006) vps25 mosaics display non-autonomous cell survival and overgrowth, and autonomous apoptosis. Development 133:1871–1880. doi: 10.1242/dev.02356 PubMedCrossRefGoogle Scholar
  84. 84.
    Igaki T, Pastor-Pareja JC, Aonuma H, Miura M, Xu T (2009) Intrinsic tumor suppression and epithelial maintenance by endocytic activation of Eiger/TNF signaling in Drosophila. Dev Cell 16:458–465. doi: 10.1016/j.devcel.2009.01.002 PubMedCrossRefGoogle Scholar
  85. 85.
    Adachi-Yamada T (2002) Puckered-GAL4 driving in JNK-active cells. Genesis 34:19–22. doi: 10.1002/gene.10110 PubMedCrossRefGoogle Scholar
  86. 86.
    Bakal C, Linding R, Llense F et al (2008) Phosphorylation networks regulating JNK activity in diverse genetic backgrounds. Science 322:453–456. doi: 10.1126/science.1158739 PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Cell Biology, G-COEKobe University Graduate School of MedicineChuo-ku, KobeJapan

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