Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway.
Drosophila provides a powerful genetic model for studying the in vivo regulation of cell death. In our large-scale gain-of-function screen, we identified Eiger, the first invertebrate tumor necrosis factor (TNF) superfamily ligand that can induce cell death. Eiger is a type II transmembrane protein with a C-terminal TNF homology domain. It is predominantly expressed in the nervous system. Genetic evidence shows that Eiger induces cell death by activating the Drosophila JNK pathway. Although this cell death process is blocked by Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), it does not require caspase activity. We also show genetically that Eiger is a physiological ligand for the Drosophila JNK pathway. Our findings demonstrate that Eiger can initiate cell death through an IAP-sensitive cell death pathway via JNK signaling.
Igaki
Tatsushi
T
Laboratory for Cell Recovery Mechanisms, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Kanda
Hiroshi
H
Yamamoto-Goto
Yuki
Y
Kanuka
Hirotaka
H
Kuranaga
Erina
E
Aigaki
Toshiro
T
Miura
Masayuki
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D017344:Genes, Insect; D017403:In Situ Hybridization; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000254:growth & development; D011506:Proteins; D016415:Sequence Alignment; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D008024:Ligands; D008565:Membrane Proteins; D010455:Peptides; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C464573:egr protein, Drosophila; C086973:rpr protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases