Signal Integration by the IκB Protein Pickle Shapes Drosophila Innate Host Defense.
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Embargo End Date
ICR Authors
Authors
Morris, O
Liu, X
Domingues, C
Runchel, C
Chai, A
Basith, S
Tenev, T
Chen, H
Choi, S
Pennetta, G
Buchon, N
Meier, P
Liu, X
Domingues, C
Runchel, C
Chai, A
Basith, S
Tenev, T
Chen, H
Choi, S
Pennetta, G
Buchon, N
Meier, P
Document Type
Journal Article
Date
2016-09-14
Date Accepted
2016-08-12
Abstract
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 Drosophila 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 pickle results in hyper-induction of Relish target genes and improved host resistance to pathogenic bacteria in the short term, chronic inactivation of pickle 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.
Citation
Cell host & microbe, 2016, 20 (3), pp. 283 - 295
Source Title
Publisher
CELL PRESS
ISSN
1931-3128
eISSN
1934-6069
Collections
Research Team
Cell Death and Immunity
Target Discovery & Apoptosis
Target Discovery & Apoptosis