Journal article
IAPs Regulate Distinct Innate Immune Pathways to Co-ordinate the Response to Bacterial Peptidoglycans
CA Stafford, KE Lawlor, VJ Heim, A Bankovacki, JP Bernardini, J Silke, U Nachbur
Cell Reports | CELL PRESS | Published : 2018
Open access
Abstract
Inhibitors of apoptosis (IAPs) proteins are critical regulators of innate immune signaling pathways and therefore have potential as drug targets. X-linked IAP (XIAP) and cellular IAP1 and IAP2 (cIAP1 and cIAP2) are E3 ligases that have been shown to be required for signaling downstream of NOD2, an intracellular receptor for bacterial peptidoglycan. We used genetic and biochemical approaches to compare the responses of IAP-deficient mice and cells to NOD2 stimulation. In all cell types tested, XIAP is the only IAP required for signaling immediately downstream of NOD2, while cIAP1 and cIAP2 are dispensable for NOD2-induced nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) a..
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Awarded by Agricultural Research Council
Funding Acknowledgements
We thank Prof. R. Flavell for the gift of Ripk2<SUP>-/-</SUP> mice, Dr. Marco Herold for the CRISPR/Cas9 constructs, Dr. Angus Stock for antibodies, Prof. C. Day for the GST-BIR2 constructs, and C. Stivala, N. Lynch, and S. Stoev for assistance with animal work. Thanks also to D. Vaux and J. Vince for suggestions and support, as well as Julie Stafford for support and proofreading. The work was supported by NHMRC grants 1046986 and 1057888 and fellowships 541901 and 1058190 to J. S. and an ARC fellowship FT130100166 to U.N. U.N. was also supported by the Swiss National Science Foundation (SNSF, fellowship PA00P3_126249). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS (9000220).