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  • The EMBO Journal (2005) 24, 3423 - 3434
  • doi:10.1038/sj.emboj.7600807

Published online: 15 September 2005

Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway

Anni Kleino1,a, Susanna Valanne1,a, Johanna Ulvila2,3, Jenni Kallio1, Henna Myllymäki1, Heidi Enwald2,3, Svenja Stöven4, Mickael Poidevin5, Ryu Ueda6, Dan Hultmark4, Bruno Lemaitre5 and Mika Rämet1,2,3,7

  1. Institute of Medical Technology, University of Tampere, Tampere, Finland
  2. Department of Pediatrics, University of Oulu, Oulu, Finland
  3. Biocenter Oulu, Oulu, Finland
  4. Umeå Centre for Molecular Pathogenesis, Umeå University, Umeå, Sweden
  5. Centre de Génétique Moléculaire, CNRS, Gif-sur-Yvette, France
  6. Genetic Strains Research Center, National Institute of Genetics, Shizuoka, Japan
  7. Department of Pediatrics, Tampere University Hospital, Tampere, Finland

Correspondence to:

Mika Rämet, Institute of Medical Technology, University of Tampere, Tampere 33014, Finland. Tel.: +358 3 35518593; Fax: +358 3 35517710; E-mail: mika.ramet@uta.fi

aThese authors contributed equally to this work

Received 17 June 2005; Accepted 17 August 2005

The Imd signaling cascade, similar to the mammalian TNF-receptor pathway, controls antimicrobial peptide expression in Drosophila. We performed a large-scale RNAi screen to identify novel components of the Imd pathway in Drosophila S2 cells. In all, 6713 dsRNAs from an S2 cell-derived cDNA library were analyzed for their effect on Attacin promoter activity in response to Escherichia coli. We identified seven gene products required for the Attacin response in vitro, including two novel Imd pathway components: inhibitor of apoptosis 2 (Iap2) and transforming growth factor-activated kinase 1 (TAK1)-binding protein (TAB). Iap2 is required for antimicrobial peptide response also by the fat body in vivo. Both these factors function downstream of Imd. Neither TAB nor Iap2 is required for Relish cleavage, but may be involved in Relish nuclear localization in vitro, suggesting a novel mode of regulation of the Imd pathway. Our results show that an RNAi-based approach is suitable to identify genes in conserved signaling cascades.

  • Keywords:

    • antimicrobial peptide expression,
    • Drosophila,
    • innate immunity,
    • RNAi screen,
    • signaling