{"doi":"10.1101/2023.02.06.527366","title":"Mono-ADP-ribosyltransferase 1 ( <i>Artc1</i> )-deficiency decreases tumorigenesis, increases inflammation, decreases cardiac contractility, and reduces survival","abstract":"Abstract Arginine-specific mono-ADP-ribosylation is a reversible post-translational modification; arginine-specific, cholera toxin-like mono-ADP-ribosyltransferases (ARTCs) transfer ADP-ribose from NAD + to arginine, followed by cleavage of ADP-ribose-(arginine)protein bond by ADP-ribosylarginine hydrolase 1 (ARH1), generating unmodified (arginine)protein. ARTC1 has been shown to enhance tumorigenicity as does Arh1 deficiency. In this study, Artc1 -KO and Artc1/Arh1 -double-KO mice showed decreased spontaneous tumorigenesis and increased age-dependent, multi-organ inflammation with upregulation of pro-inflammatory cytokine TNF- α . In a xenograft model using tumorigenic Arh1 -KO mouse embryonic fibroblasts (MEFs), tumorigenicity was decreased in Artc1 -KO and heterozygous recipient mice, with tumor infiltration by CD8 + T cells and macrophages, leading to necroptosis, suggesting that ARTC1 promotes the tumor microenvironment. Furthermore, Artc1/Arh1 -double-KO MEFs showed decreased tumorigenesis in nude mice, showing that tumor cells as well as tumor microenvironment require ARTC1. By echocardiography and MRI, Artc1 -KO and heterozygous mice showed male-specific, reduced myocardial contractility. Furthermore, Artc1 -KO male hearts exhibited enhanced susceptibility to myocardial ischemia-reperfusion-induced injury with increased receptor-interacting protein kinase 3 (RIP3) protein levels compared to WT mice, suggesting that ARTC1 suppresses necroptosis. Overall survival rate of Artc1 -KO was less than their Artc1 -WT counterparts, primarily due to enhanced immune response and inflammation. Thus, anti-ARTC1 agents may reduce tumorigenesis but may increase multi-organ inflammation and decrease cardiac contractility. Graphical Abstract","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":402876,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":241248,"name":"Jiro Kato","orcid":"0000-0003-0318-1794","position":1,"is_corresponding":false},{"id":1180450,"name":"Hirotake Oda","orcid":"0000-0001-7962-7938","position":2,"is_corresponding":false},{"id":461835,"name":"Junhui Sun","orcid":"0000-0002-1816-1190","position":3,"is_corresponding":false},{"id":265814,"name":"Zu‐Xi Yu","orcid":"0000-0003-1141-4551","position":4,"is_corresponding":false},{"id":242699,"name":"Chengyu Liu","orcid":"0000-0002-5136-9225","position":5,"is_corresponding":false},{"id":299704,"name":"Danielle Springer","orcid":"0000-0002-6261-9744","position":6,"is_corresponding":false},{"id":271933,"name":"Pradeep K. Dagur","orcid":"0000-0002-4491-0853","position":7,"is_corresponding":false},{"id":788237,"name":"Martin J. Lizak","orcid":null,"position":8,"is_corresponding":false},{"id":228250,"name":"Elizabeth Murphy","orcid":"0000-0001-9400-0797","position":9,"is_corresponding":false},{"id":241249,"name":"Joel Moss","orcid":"0000-0003-1788-1927","position":10,"is_corresponding":false},{"id":431635,"name":"Hiroko Ishiwata-Endo","orcid":"0000-0002-9962-8206","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T01:20:32.588152Z","pmid":"36945646","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":[]}