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Publication : BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella.

First Author  Andree M Year  2014
Journal  EMBO J Volume  33
Issue  19 Pages  2171-87
PubMed ID  25056906 Mgi Jnum  J:214844
Mgi Id  MGI:5604070 Doi  10.15252/embj.201387244
Citation  Andree M, et al. (2014) BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella. EMBO J 33(19):2171-87
abstractText  The X-linked inhibitor of apoptosis protein (XIAP) is a potent caspase inhibitor, best known for its anti-apoptotic function in cancer. During apoptosis, XIAP is antagonized by SMAC, which is released from the mitochondria upon caspase-mediated activation of BID. Recent studies suggest that XIAP is involved in immune signaling. Here, we explore XIAP as an important mediator of an immune response against the enteroinvasive bacterium Shigella flexneri, both in vitro and in vivo. Our data demonstrate for the first time that Shigella evades the XIAP-mediated immune response by inducing the BID-dependent release of SMAC from the mitochondria. Unlike apoptotic stimuli, Shigella activates the calpain-dependent cleavage of BID to trigger the release of SMAC, which antagonizes the inflammatory action of XIAP without inducing apoptosis. Our results demonstrate how the cellular death machinery can be subverted by an invasive pathogen to ensure bacterial colonization.
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