{"doi":"10.1038/ncomms15556","title":"The PYRIN domain-only protein POP2 inhibits inflammasome priming and activation","abstract":"<jats:title>Abstract</jats:title><jats:p>Inflammasomes are protein platforms linking recognition of microbe, pathogen-associated and damage-associated molecular patterns by cytosolic sensory proteins to caspase-1 activation. Caspase-1 promotes pyroptotic cell death and the maturation and secretion of interleukin (IL)-1β and IL-18, which trigger inflammatory responses to clear infections and initiate wound-healing; however, excessive responses cause inflammatory disease. Inflammasome assembly requires the PYRIN domain (PYD)-containing adaptor ASC, and depends on PYD–PYD interactions. Here we show that the PYD-only protein POP2 inhibits inflammasome assembly by binding to ASC and interfering with the recruitment of ASC to upstream sensors, which prevents caspase-1 activation and cytokine release. POP2 also impairs macrophage priming by inhibiting the activation of non-canonical IκB kinase ɛ and IκBα, and consequently protects from excessive inflammation and acute shock <jats:italic>in vivo</jats:italic>. Our findings advance our understanding of the complex regulatory mechanisms that maintain a balanced inflammatory response and highlight important differences between individual POP members.</jats:p>","journal":"Nature Communications","year":2017,"id":635343,"datarank":0.6090664515819629,"base_score":4.060443010546419,"endowment":4.060443010546419,"self_citation_contribution":0.6090664515819629,"citation_network_contribution":0.0,"self_endowment_contribution":0.6090664515819629,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":57,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":842287,"name":"Lan H. Chu","orcid":"0000-0002-0378-6614","position":1,"is_corresponding":false},{"id":1190381,"name":"Sonal Khare","orcid":"0000-0002-4044-3581","position":2,"is_corresponding":false},{"id":1648325,"name":"Lucia de Almeida","orcid":null,"position":3,"is_corresponding":false},{"id":861124,"name":"Anu Gangopadhyay","orcid":null,"position":4,"is_corresponding":false},{"id":880346,"name":"Mohanalaxmi Indramohan","orcid":null,"position":5,"is_corresponding":false},{"id":569803,"name":"Alexander V. Misharin","orcid":"0000-0002-3068-9676","position":6,"is_corresponding":false},{"id":230516,"name":"David R. 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Caspase-1 promotes pyroptotic cell death and the maturation and secretion of interleukin (IL)-1β and IL-18, which trigger inflammatory responses to clear infections and initiate wound-healing; however, excessive responses cause inflammatory disease. Inflammasome assembly requires the PYRIN domain (PYD)-containing adaptor ASC, and depends on PYD–PYD interactions. Here we show that the PYD-only protein POP2 inhibits inflammasome assembly by binding to ASC and interfering with the recruitment of ASC to upstream sensors, which prevents caspase-1 activation and cytokine release. POP2 also impairs macrophage priming by inhibiting the activation of non-canonical IκB kinase ɛ and IκBα, and consequently protects from excessive inflammation and acute shock <jats:italic>in vivo</jats:italic>. Our findings advance our understanding of the complex regulatory mechanisms that maintain a balanced inflammatory response and highlight important differences between individual POP members.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28580931","pmcid":"PMC5465353","openalex_id":null,"authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI120618","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"T32 AR007611","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"P30 AR057216","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR064546","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"K01 AR066739","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA060553","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI120625","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL134375","title":null},{"funder_name":"British Heart Foundation","grant_id":"RG/15/10/31485","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI099009","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR064349","title":null}],"total_grants":11,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/ncomms15556.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/ncomms15556","host_type":"publisher"},{"url":"http://www.nature.com/doifinder/10.1038/ncomms15556","host_type":"publisher"},{"url":"https://doaj.org/article/28458afcf61a49ae89fbff053e45bdf4","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5465353","host_type":"repository"},{"url":"https://ora.ox.ac.uk/objects/uuid:e00aaa9e-c18d-478d-b249-8d8cbeba1f3c","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5465353","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5465353?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["Macrophages","Animals","Mice, Transgenic","Humans","Mice","Inflammation","Caspase 1","Adaptor Proteins, Signal Transducing","Nuclear Proteins","Interleukin-18","Cytokines","Flow Cytometry","Enzyme Activation","I-kappa B Kinase","Interleukin-1beta","Inflammasomes","Pyroptosis","Pyrin Domain"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:58:03.973550Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}