| http://purl.uniprot.org/citations/36414671 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36414671 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of RIPK1-driven cell death and inflammation play important roles in the progression of nonalcoholic steatohepatitis (NASH). However, the mechanism underlying RIPK1 activation in NASH remains unclear. Here we identified SENP1, a SUMO-specific protease, as a key endogenous inhibitor of RIPK1. SENP1 is progressively reduced in proportion to NASH severity in patients. Hepatocyte-specific SENP1-knockout mice develop spontaneous NASH-related phenotypes in a RIPK1 kinase-dependent manner. We demonstrate that SENP1 deficiency sensitizes cells to RIPK1 kinase-dependent apoptosis by promoting RIPK1 activation following TNFα stimulation. Mechanistically, SENP1 deSUMOylates RIPK1 in TNF-R1 signaling complex (TNF-RSC), keeping RIPK1 in check. Loss of SENP1 leads to SUMOylation of RIPK1, which re-orchestrates TNF-RSC and modulates the ubiquitination patterns and activity of RIPK1. Notably, genetic inhibition of RIPK1 effectively reverses disease progression in hepatocyte-specific SENP1-knockout male mice with high-fat-diet-induced nonalcoholic fatty liver. We propose that deSUMOylation of RIPK1 by SENP1 provides a pathophysiologically relevant cell death-restricting checkpoint that modulates RIPK1 activation in the pathogenesis of nonalcoholic steatohepatitis."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-022-34993-0"xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Chen Z."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Gu J."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Liu N."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Sun Q."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Xu D."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Zhong Y."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Zhang T."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Yan L."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Yang Y."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Wang K."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Zhang M."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/author | "Shan B."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/name | "Nat Commun"xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/pages | "7153"xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/title | "SENP1 prevents steatohepatitis by suppressing RIPK1-driven apoptosis and inflammation."xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://purl.uniprot.org/core/volume | "13"xsd:string |
| http://purl.uniprot.org/citations/36414671 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/36414671 |
| http://purl.uniprot.org/citations/36414671 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/36414671 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JGF4-mappedCitation-36414671 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36414671 |
| http://purl.uniprot.org/uniprot/#_A0A087WPS3-mappedCitation-36414671 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36414671 |