| First Author | Yabal M | Year | 2014 |
| Journal | Cell Rep | Volume | 7 |
| Issue | 6 | Pages | 1796-808 |
| PubMed ID | 24882010 | Mgi Jnum | J:211783 |
| Mgi Id | MGI:5576402 | Doi | 10.1016/j.celrep.2014.05.008 |
| Citation | Yabal M, et al. (2014) XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation. Cell Rep 7(6):1796-808 |
| abstractText | X-linked inhibitor of apoptosis protein (XIAP) has been identified as a potent regulator of innate immune responses, and loss-of-function mutations in XIAP cause the development of the X-linked lymphoproliferative syndrome type 2 (XLP-2) in humans. Using gene-targeted mice, we show that loss of XIAP or deletion of its RING domain lead to excessive cell death and IL-1beta secretion from dendritic cells triggered by diverse Toll-like receptor stimuli. Aberrant IL-1beta secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2. The observed cell death also requires TNF and RIP3 but proceeds independently of caspase-1/caspase-11 or caspase-8 function. Loss of XIAP results in aberrantly elevated ubiquitylation of RIP1 outside of TNFR complex I. Virally infected Xiap(-/-) mice present with symptoms reminiscent of XLP-2. Our data show that XIAP controls RIP3-dependent cell death and IL-1beta secretion in response to TNF, which might contribute to hyperinflammation in patients with XLP-2. |
