Journal
TRENDS IN MOLECULAR MEDICINE
Volume 20, Issue 11, Pages 652-665Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2014.09.006
Keywords
anti-apoptotic proteins; inflammation; inflammatory bowel disease; intestine; signaling pathways; ubiquitin ligases
Funding
- Danish Council for Independent Research, Health and Disease
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The inhibitor of apoptosis (IAP) family members, notably clAP1, clAP2, and XIAP, are critical and universal regulators of tumor necrosis factor (TNF) mediated survival, inflammatory, and death signaling pathways. Furthermore, IAPs mediate the signaling of nucleotide-binding oligomerization domain (NOD)1/NOD2 and other intracellular NOD-like receptors in response to bacterial pathogens. These pathways are important to the pathogenesis and treatment of inflammatory bowel disease (IBD). Inactivating mutations in the X-chromosome-linked IAP (XIAP) gene causes an immunodeficiency syndrome, X-linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected, and may have therapeutic potential.
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