{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:39:05Z","timestamp":1768505945535,"version":"3.49.0"},"posted":{"date-parts":[[2023,2,6]]},"group-title":"Cancer Biology","reference-count":79,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,2,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:sup>+<\/jats:sup>\n                  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\n                  <jats:italic>Arh1<\/jats:italic>\n                  deficiency. In this study,\n                  <jats:italic>Artc1<\/jats:italic>\n                  -KO and\n                  <jats:italic>Artc1\/Arh1<\/jats:italic>\n                  -double-KO mice showed decreased spontaneous tumorigenesis and increased age-dependent, multi-organ inflammation with upregulation of pro-inflammatory cytokine TNF-\n                  <jats:italic>\u03b1<\/jats:italic>\n                  . In a xenograft model using tumorigenic\n                  <jats:italic>Arh1<\/jats:italic>\n                  -KO mouse embryonic fibroblasts (MEFs), tumorigenicity was decreased in\n                  <jats:italic>Artc1<\/jats:italic>\n                  -KO and heterozygous recipient mice, with tumor infiltration by CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells and macrophages, leading to necroptosis, suggesting that ARTC1 promotes the tumor microenvironment. Furthermore,\n                  <jats:italic>Artc1\/Arh1<\/jats:italic>\n                  -double-KO MEFs showed decreased tumorigenesis in nude mice, showing that tumor cells as well as tumor microenvironment require ARTC1. By echocardiography and MRI,\n                  <jats:italic>Artc1<\/jats:italic>\n                  -KO and heterozygous mice showed male-specific, reduced myocardial contractility. Furthermore,\n                  <jats:italic>Artc1<\/jats:italic>\n                  -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\n                  <jats:italic>Artc1<\/jats:italic>\n                  -KO was less than their\n                  <jats:italic>Artc1<\/jats:italic>\n                  -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.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"527366v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2023.02.06.527366","type":"posted-content","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T22:50:11Z","timestamp":1675723811000},"source":"Crossref","is-referenced-by-count":0,"title":["Mono-ADP-ribosyltransferase 1 (\n                  <i>Artc1<\/i>\n                  )-deficiency decreases tumorigenesis, increases inflammation, decreases cardiac contractility, and reduces survival"],"prefix":"10.64898","author":[{"given":"Hiroko","family":"Ishiwata-Endo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiro","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotake","family":"Oda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zu-Xi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle A.","family":"Springer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep","family":"Dagur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J.","family":"Lizak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Moss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023020818551234000_2023.02.06.527366v1.1","unstructured":"Fishman PH . 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