| http://purl.uniprot.org/citations/34887354 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34887354 | http://www.w3.org/2000/01/rdf-schema#comment | "SHARPIN, together with RNF31/HOIP and RBCK1/HOIL1, form the linear ubiquitin chain assembly complex (LUBAC) E3 ligase that catalyzes M1-linked polyubiquitination. Mutations in RNF31/HOIP and RBCK/HOIL1 in humans and Sharpin in mice lead to autoinflammation and immunodeficiency, but the mechanism underlying the immune dysregulation remains unclear. We now show that the phenotype of the Sharpincpdm/cpdm mice is dependent on CYLD, a deubiquitinase previously shown to mediate removal of K63-linked polyubiquitin chains. Dermatitis, disrupted splenic architecture, and loss of Peyer's patches in the Sharpincpdm/cpdm mice were fully reversed in Sharpincpdm/cpdm Cyld-/- mice. We observed enhanced association of RIPK1 with the death-signaling Complex II following TNF stimulation in Sharpincpdm/cpdm cells, a finding dependent on CYLD since we observed reversal in Sharpincpdm/cpdm Cyld-/- cells. Enhanced RIPK1 recruitment to Complex II in Sharpincpdm/cpdm cells correlated with impaired phosphorylation of CYLD at serine 418, a modification reported to inhibit its enzymatic activity. The dermatitis in the Sharpincpdm/cpdm mice was also ameliorated by the conditional deletion of Cyld using LysM-cre or Cx3cr1-cre indicating that CYLD-dependent death of myeloid cells is inflammatory. Our studies reveal that under physiological conditions, TNF- and RIPK1-dependent cell death is suppressed by the linear ubiquitin-dependent inhibition of CYLD. The Sharpincpdm/cpdm phenotype illustrates the pathological consequences when CYLD inhibition fails."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2001602118"xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Xiong H."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Ang R.L."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Sundberg J.P."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Chan M."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Sun S.C."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Lira S.A."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Heeger P.S."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Ting A.T."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Chun N."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Legarda D."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/author | "Gillespie V.L."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/pages | "e2001602118"xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/title | "Immune dysregulation in SHARPIN-deficient mice is dependent on CYLD-mediated cell death."xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://purl.uniprot.org/core/volume | "118"xsd:string |
| http://purl.uniprot.org/citations/34887354 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34887354 |
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| http://purl.uniprot.org/uniprot/#_E0CZH2-mappedCitation-34887354 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34887354 |
| http://purl.uniprot.org/uniprot/#_A0A1B0GSE5-mappedCitation-34887354 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34887354 |
| http://purl.uniprot.org/uniprot/#_F6UHH8-mappedCitation-34887354 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34887354 |