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  • The EMBO Journal (2002) 21, 3009 - 3018
  • doi:10.1093/emboj/cdf306

Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway

Tatsushi Igaki1,2, Hiroshi Kanda1,3, Yuki Yamamoto-Goto1, Hirotaka Kanuka1, Erina Kuranaga1,2, Toshiro Aigaki4 and Masayuki Miura1

  1. Laboratory for Cell Recovery Mechanisms, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
  2. Department of Cell Biology and Neuroscience Hachioji, Tokyo 192-0397, Japan
  3. Division of Molecular Genetics, Osaka University Graduate School of Medicine, 1-3 Yamadaoka, Suita, Osaka 565-0871 Japan
  4. Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji, Tokyo 192-0397, Japan

Correspondence to:

Masayuki Miura, E-mail: miura@brain.riken.go.jp

Received 22 March 2002; Accepted 29 April 2002; Revised 29 April 2002

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.

  • Keywords:

    • cell death,
    • Drosophila,
    • JNK,
    • TNF