| http://purl.uniprot.org/citations/27819682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27819682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27819682 | http://www.w3.org/2000/01/rdf-schema#comment | "Receptor-interacting protein kinase 1 (RIPK1) promotes cell survival-mice lacking RIPK1 die perinatally, exhibiting aberrant caspase-8-dependent apoptosis and mixed lineage kinase-like (MLKL)-dependent necroptosis. However, mice expressing catalytically inactive RIPK1 are viable, and an ill-defined pro-survival function for the RIPK1 scaffold has therefore been proposed. Here we show that the RIP homotypic interaction motif (RHIM) in RIPK1 prevents the RHIM-containing adaptor protein ZBP1 (Z-DNA binding protein 1; also known as DAI or DLM1) from activating RIPK3 upstream of MLKL. Ripk1RHIM/RHIM mice that expressed mutant RIPK1 with critical RHIM residues IQIG mutated to AAAA died around birth and exhibited RIPK3 autophosphorylation on Thr231 and Ser232, which is a hallmark of necroptosis, in the skin and thymus. Blocking necroptosis with catalytically inactive RIPK3(D161N), RHIM mutant RIPK3, RIPK3 deficiency, or MLKL deficiency prevented lethality in Ripk1RHIM/RHIM mice. Loss of ZBP1, which engages RIPK3 in response to certain viruses but previously had no defined role in development, also prevented perinatal lethality in Ripk1RHIM/RHIM mice. Consistent with the RHIM of RIPK1 functioning as a brake that prevents ZBP1 from engaging the RIPK3 RHIM, ZBP1 interacted with RIPK3 in Ripk1RHIM/RHIMMlkl-/- macrophages, but not in wild-type, Mlkl-/- or Ripk1RHIM/RHIMRipk3RHIM/RHIM macrophages. Collectively, these findings indicate that the RHIM of RIPK1 is critical for preventing ZBP1/RIPK3/MLKL-dependent necroptosis during development."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature20559"xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature20559"xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Roose-Girma M."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Roose-Girma M."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Dixit V.M."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Dixit V.M."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Newton K."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Newton K."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Strasser A."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Strasser A."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Ngu H."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Ngu H."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Lill J.R."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Lill J.R."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Dugger D.L."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Dugger D.L."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Warming S."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Warming S."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Maltzman A."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Maltzman A."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Pham V.C."xsd:string |
| http://purl.uniprot.org/citations/27819682 | http://purl.uniprot.org/core/author | "Pham V.C."xsd:string |