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- 저자 : Runchel, Christopher (검색결과 1 건)
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Signal Integration by the IκB Protein Pickle Shapes <i>Drosophila</i> Innate Host Defense
Morris, Otto,Liu, Xi,Domingues, Celia,Runchel, Christopher,Chai, Andrea,Basith, Shaherin,Tenev, Tencho,Chen, Haiyang,Choi, Sangdun,Pennetta, Giuseppa,Buchon, Nicolas,Meier, Pascal Cell Press 2016 Cell host & microbe Vol.20 No.3
<▼1><P><B>Summary</B></P><P>Pattern recognition receptors are activated following infection and trigger transcriptional programs important for host defense. Tight regulation of NF-κB activation is critical to avoid detrimental and misbalanced responses. We describe Pickle, a <I>Drosophila</I> nuclear IκB that integrates signaling inputs from both the Imd and Toll pathways by skewing the transcriptional output of the NF-κB dimer repertoire. Pickle interacts with the NF-κB protein Relish and the histone deacetylase dHDAC1, selectively repressing Relish homodimers while leaving other NF-κB dimer combinations unscathed. Pickle’s ability to selectively inhibit Relish homodimer activity contributes to proper host immunity and organismal health. Although loss of <I>pickle</I> results in hyper-induction of Relish target genes and improved host resistance to pathogenic bacteria in the short term, chronic inactivation of <I>pickle</I> causes loss of immune tolerance and shortened lifespan. Pickle therefore allows balanced immune responses that protect from pathogenic microbes while permitting the establishment of beneficial commensal host-microbe relationships.</P></▼1><▼2><P><B>Highlights</B></P><P>•<P>Pickle selectively inhibits NF-κB target genes that are driven by Relish homodimers</P>•<P>Pickle is a nuclear member of the IκB protein family</P>•<P>Loss of <I>pickle</I> causes hyper-activation of Relish-dependent target genes</P>•<P>Loss of <I>pickle</I> enhances host resistance to bacteria but compromises lifespan</P></P></▼2><▼3><P>Tight regulation of NF-κB signaling is critical to avoid detrimental and misbalanced responses. Morris et al. identify an IκB protein in <I>Drosophila</I> that inhibits a selective subset of the NF-κB dimer repertoire, thereby ensuring an appropriate immune response to pathogens while preventing tissue damage and reduced lifespan.</P></▼3>
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