Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Jost, PJ; Vucic, D.
Regulation of Cell Death and Immunity by XIAP.
JACC-CARDIOVASC INTE. 2020; 13(15): a036426
Doi: 10.1101/cshperspect.a036426
Web of Science
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- Führende Autor*innen der Med Uni Graz
- Jost Philipp
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- Abstract:
- X-chromosome-linked inhibitor of apoptosis protein (XIAP) controls cell survival in several regulated cell death pathways and coordinates a range of inflammatory signaling events. Initially identified as a caspase-binding protein, it was considered to be primarily involved in blocking apoptosis from both intrinsic as well as extrinsic triggers. However, XIAP also prevents TNF-mediated, receptor-interacting protein 3 (RIPK3)-dependent cell death, by controlling RIPK1 ubiquitylation and preventing inflammatory cell death. The identification of patients with germline mutations in XIAP (termed XLP-2 syndrome) pointed toward its role in inflammatory signaling. Indeed, XIAP also mediates nucleotide-binding oligomerization domain-containing 2 (NOD2) proinflammatory signaling by promoting RIPK2 ubiquitination within the NOD2 signaling complex leading to NF-kappa B and MAPK activation and production of inflammatory cytokines and chemokines. Overall, XIAP is a critical regulator of multiple cell death and inflammatory pathways making it an attractive drug target in tumors and inflammatory diseases.