{"doi":"10.1016/j.celrep.2024.114335","title":"The interaction between RIPK1 and FADD controls perinatal lethality and inflammation","abstract":"Perturbation of the apoptosis and necroptosis pathways critically influences embryogenesis. Receptor-associated protein kinase-1 (RIPK1) interacts with Fas-associated via death domain (FADD)-caspase-8-cellular Flice-like inhibitory protein long (cFLIP L ) to regulate both extrinsic apoptosis and necroptosis. Here, we describe Ripk1 -mutant animals ( Ripk1 R588E [RE]) in which the interaction between FADD and RIPK1 is disrupted, leading to embryonic lethality. This lethality is not prevented by further removal of the kinase activity of Ripk1 ( Ripk1 R588E K45A [REKA]). Both Ripk1 RE and Ripk1 REKA animals survive to adulthood upon ablation of Ripk3 . While embryonic lethality of Ripk1 RE mice is prevented by ablation of the necroptosis effector mixed lineage kinase-like (MLKL), animals succumb to inflammation after birth. In contrast, Mlkl ablation does not prevent the death of Ripk1 REKA embryos, but animals reach adulthood when both MLKL and caspase-8 are removed. Ablation of the nucleic acid sensor Zbp1 largely prevents lethality in both Ripk1 RE and Ripk1 REKA embryos. Thus, the RIPK1-FADD interaction prevents Z-DNA binding protein-1 (ZBP1)-induced, RIPK3-caspase-8-mediated embryonic lethality, affected by the kinase activity of RIPK1.","journal":"Cell Reports","year":2024,"id":438501,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":225729,"name":"Bart Tummers","orcid":"0000-0001-7580-778X","position":1,"is_corresponding":false},{"id":410987,"name":"Jeremy J.P. Shaw","orcid":"0000-0002-7458-215X","position":2,"is_corresponding":false},{"id":225724,"name":"Giovanni Quarato","orcid":"0000-0003-1167-3422","position":3,"is_corresponding":false},{"id":1248640,"name":"Ricardo Weinlich","orcid":"0000-0001-6822-7330","position":4,"is_corresponding":false},{"id":1249176,"name":"James G. Cripps","orcid":null,"position":5,"is_corresponding":false},{"id":252506,"name":"Patrick Fitzgerald","orcid":"0000-0003-0674-6420","position":6,"is_corresponding":false},{"id":252507,"name":"Laura J. Janke","orcid":"0000-0002-9871-6239","position":7,"is_corresponding":false},{"id":252508,"name":"S. William Pelletier","orcid":"0000-0002-1127-0212","position":8,"is_corresponding":false},{"id":225728,"name":"Jeremy Chase Crawford","orcid":"0000-0003-4096-6048","position":9,"is_corresponding":false},{"id":225738,"name":"Douglas R. Green","orcid":"0000-0002-7332-1417","position":10,"is_corresponding":false},{"id":225730,"name":"Diego A. Rodríguez","orcid":"0000-0003-4771-0221","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:00:43.618468Z","pmid":"38850531","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":[]}