Research ArticleHost-Microbe Interactions

Transglutaminase-Catalyzed Protein-Protein Cross-Linking Suppresses the Activity of the NF-κB–Like Transcription Factor Relish

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Science Signaling  23 Jul 2013:
Vol. 6, Issue 285, pp. ra61
DOI: 10.1126/scisignal.2003970

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Tolerating Commensals

The Drosophila gut contains various species of nonpathogenic, commensal microbes that contribute to immune homeostasis and metabolism. Shibata et al. found that the enzyme transglutaminase, which cross-links various protein substrates, was key in suppressing inappropriate immune responses to these commensal microbes. Transglutaminase cross-linked and inactivated Relish, a homolog of the NF-κB family of transcription factors, which in flies contributes to the production of antimicrobial peptides. Knocking down transglutaminase in flies caused a shorter life span, and inhibiting the function of transglutaminase in flies increased the production of antimicrobial peptides. Thus, transglutaminase-mediated cross-linking of Relish suppresses immune responses to gut commensal bacteria in Drosophila.