{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["19(10)"],"submitter":["Zhuang W"],"pubmed_abstract":["Inflammasomes are essential components of the innate immune system and its defense against infections, whereas the dysregulation of inflammasome activation has a detrimental effect on human health. The activation of inflammasomes is subjected to tight regulation to maintain immune homeostasis, yet the underlying mechanism remains elusive. Here, we identify USP3 as a direct deubiquitinating enzyme (DUB) for ASC, the central adapter mediating the assembly and activation of most inflammasomes. USP3 removes the K48-linked ubiquitination on ASC and strengthens its stability by blocking proteasomal degradation. Additionally, USP3 promotes inflammasome activation, and this function was confirmed in mouse models of aluminum (Alum)-induced peritonitis, F. novicida infection and flagellin-induced pneumonia in vivo. Our work unveils that USP3 functions as a key regulator of ASC ubiquitination and maintains the physiological role of ASC in mediating inflammasome activation, and we propose a new mechanism by which the ubiquitination of ASC regulates inflammasome activation."],"journal":["Cellular & molecular immunology"],"pagination":["1141-1152"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9508167"],"repository":["biostudies-literature"],"pubmed_title":["USP3 deubiquitinates and stabilizes the adapter protein ASC to regulate inflammasome activation."],"pmcid":["PMC9508167"],"pubmed_authors":["Zheng Y","Ma C","Zhao W","Zhuang W","Liu B","Zhang L","Liu S","Liu F","Gao C"],"additional_accession":[]},"is_claimable":false,"name":"USP3 deubiquitinates and stabilizes the adapter protein ASC to regulate inflammasome activation.","description":"Inflammasomes are essential components of the innate immune system and its defense against infections, whereas the dysregulation of inflammasome activation has a detrimental effect on human health. The activation of inflammasomes is subjected to tight regulation to maintain immune homeostasis, yet the underlying mechanism remains elusive. Here, we identify USP3 as a direct deubiquitinating enzyme (DUB) for ASC, the central adapter mediating the assembly and activation of most inflammasomes. USP3 removes the K48-linked ubiquitination on ASC and strengthens its stability by blocking proteasomal degradation. Additionally, USP3 promotes inflammasome activation, and this function was confirmed in mouse models of aluminum (Alum)-induced peritonitis, F. novicida infection and flagellin-induced pneumonia in vivo. Our work unveils that USP3 functions as a key regulator of ASC ubiquitination and maintains the physiological role of ASC in mediating inflammasome activation, and we propose a new mechanism by which the ubiquitination of ASC regulates inflammasome activation.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2025-04-18T23:54:15.977Z","creation":"2025-04-07T11:15:26.722Z"},"accession":"S-EPMC9508167","cross_references":{"pubmed":["36050480"],"doi":["10.1038/s41423-022-00917-7"]}}