| First Author | Krieg A | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 34 | Pages | 14524-9 |
| PubMed ID | 19667203 | Mgi Jnum | J:151941 |
| Mgi Id | MGI:4355611 | Doi | 10.1073/pnas.0907131106 |
| Citation | Krieg A, et al. (2009) XIAP mediates NOD signaling via interaction with RIP2. Proc Natl Acad Sci U S A 106(34):14524-9 |
| abstractText | NOD1 and NOD2 are members of the NOD-like receptor (NLR) protein family that are involved in sensing the presence of pathogens and are a component of the innate immune system. Upon activation by specific bacterial peptides derived from peptidoglycans, NODs interact via a CARD-CARD interaction with the receptor-interacting protein kinase RIP2, an inducer of NF-kappaB activation. In this report, we show that NOD signaling is dependent on XIAP, a member of the inhibitor of apoptosis protein (IAP) family. Cells deficient in XIAP exhibit a marked reduction in NF-kappaB activation induced by microbial NOD ligands and by over-expression of NOD1 or NOD2. Moreover, we show that XIAP interacts with RIP2 via its BIR2 domain, which could be disrupted by XIAP antagonists SMAC and SMAC-mimicking compounds. Both NOD1 and NOD2 associated with XIAP in a RIP2-dependent manner, providing evidence that XIAP associates with the NOD signalosome. Taken together, our data suggest a role for XIAP in regulating innate immune responses by interacting with NOD1 and NOD2 through interaction with RIP2. |
