| http://purl.uniprot.org/citations/29695863 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29695863 | http://www.w3.org/2000/01/rdf-schema#comment | "The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR1 1 . Deficiency in the LUBAC components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-mediated cell death2-8. In humans, deficiency in the third LUBAC component HOIL-1 causes autoimmunity and inflammatory disease, similar to HOIP deficiency, whereas HOIL-1 deficiency in mice was reported to cause no overt phenotype9-11. Here we show, by creating HOIL-1-deficient mice, that HOIL-1 is as essential for LUBAC function as HOIP, albeit for different reasons: whereas HOIP is the catalytically active component of LUBAC, HOIL-1 is required for LUBAC assembly, stability and optimal retention in the TNFR1 signalling complex, thereby preventing aberrant cell death. Both HOIL-1 and HOIP prevent embryonic lethality at mid-gestation by interfering with aberrant TNFR1-mediated endothelial cell death, which only partially depends on RIPK1 kinase activity. Co-deletion of caspase-8 with RIPK3 or MLKL prevents cell death in Hoil-1-/- (also known as Rbck1-/-) embryos, yet only the combined loss of caspase-8 with MLKL results in viable HOIL-1-deficient mice. Notably, triple-knockout Ripk3-/-Casp8-/-Hoil-1-/- embryos die at late gestation owing to haematopoietic defects that are rescued by co-deletion of RIPK1 but not MLKL. Collectively, these results demonstrate that both HOIP and HOIL-1 are essential LUBAC components and are required for embryogenesis by preventing aberrant cell death. Furthermore, they reveal that when LUBAC and caspase-8 are absent, RIPK3 prevents RIPK1 from inducing embryonic lethality by causing defects in fetal haematopoiesis."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41586-018-0064-8"xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Shimizu Y."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Draber P."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Bertin J."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Fisher A."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Haas T.L."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Walczak H."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Bouillet P."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Strasser A."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Darding M."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Silke J."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Alvarez-Diaz S."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Enver T."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Sarr A."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Draberova H."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Hartwig T."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Kupka S."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Lafont E."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Rieser E."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Taraborrelli L."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Kaiser W."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Hutchinson C."xsd:string |
| http://purl.uniprot.org/citations/29695863 | http://purl.uniprot.org/core/author | "Boiers C."xsd:string |