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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >XIAP mediates NOD signaling via interaction with RIP2
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XIAP mediates NOD signaling via interaction with RIP2

机译：XIAP通过与RIP2的相互作用介导NOD信号传导

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摘要

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-κB 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-kB activation induced by microbial NOD ligands and by over-expression of N0D1 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.
机译：NOD1和NOD2是NOD样受体（NLR）蛋白家族的成员，参与感测病原体的存在，并且是先天免疫系统的组成部分。通过衍生自肽聚糖的特定细菌肽激活后，NOD通过CARD-CARD相互作用与受体相互作用的蛋白激酶RIP2（NF-κB激活的诱导剂）相互作用。在此报告中，我们显示NOD信号依赖于XIAP，XIAP是凋亡蛋白（IAP）家族抑制剂的成员。 XIAP缺陷的细胞在微生物NOD配体和过表达N0D1或NOD2的诱导下，NF-kB活化显着降低。此外，我们显示XIAP通过其BIR2域与RIP2相互作用，这可能被XIAP拮抗剂SMAC和SMAC模拟化合物破坏。 NOD1和NOD2都以依赖RIP2的方式与XIAP相关，这提供了XIAP与NOD信号体相关的证据。两者合计，我们的数据表明XIAP通过与RIP2相互作用与NOD1和NOD2相互作用，在调节先天免疫应答中发挥作用。

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    Andreas Krieg; Ricardo G. Correa; Jason B. Garrison; Gaeelle Le Negrate; Kate Welsh; Ziwei Huang; Wolfram T. Knoefel; John C. Reed;

  • 作者单位

    Burnham Institute for Medical Research, La Jolla, CA 92037 Department of General, Visceral and Pediatric Surgery, University Hospital Duesseldorf, D-40225 Duesseldorf, Germany;

    Burnham Institute for Medical Research, La Jolla, CA 92037;

    Burnham Institute for Medical Research, La Jolla, CA 92037;

    Burnham Institute for Medical Research, La Jolla, CA 92037 lnstitute of Medical Microbiology and Hospital Hygiene, University Hospital Duessledorf, D40225 Duesseldorf, Germany;

    Burnham Institute for Medical Research, La Jolla, CA 92037;

    Burnham Institute for Medical Research, La Jolla, CA 92037;

    Department of General, Visceral and Pediatric Surgery, University Hospital Duesseldorf, D-40225 Duesseldorf, Germany;

    Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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