{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:46:30Z","timestamp":1777949190599,"version":"3.51.4"},"posted":{"date-parts":[[2023,2,7]]},"group-title":"Cancer Biology","reference-count":47,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  ADP-ribosylation is a reversible reaction with ADP-ribosyltransferases catalyzing the forward reaction and ADP-ribose-acceptor hydrolases (ARHs) hydrolyzing the ADP-ribose acceptor bond. ARH2 is a member of the 39-kDa ARH family (ARH1-3), which is expressed in heart and skeletal muscle. ARH2 failed to exhibit any in vitro enzymatic activity. To determine its possible in vivo activities,\n                  <jats:italic>Arh2<\/jats:italic>\n                  -knockout (KO) and - heterozygous (Het) mice were generated using CRISPR-Cas9.\n                  <jats:italic>Arh2<\/jats:italic>\n                  -KO mice exhibited decreased cardiac contractility by MRI, echocardiography and dobutamine stress with cardiomegaly and abnormal motor function.\n                  <jats:italic>Arh2<\/jats:italic>\n                  -Het mice showed results similar to those seen in\n                  <jats:italic>Arh2<\/jats:italic>\n                  -KO mice except for cardiomegaly.\n                  <jats:italic>Arh2<\/jats:italic>\n                  -KO and -Het mice and mouse embryonic fibroblasts (MEFs) developed spontaneous tumors and subcutaneous tumors in nude mice. We identified 13 mutations in\n                  <jats:italic>Arh2<\/jats:italic>\n                  -Het MEFs and heterozygous tumors, corresponding to human\n                  <jats:italic>ARH2<\/jats:italic>\n                  mutations in cancers obtained from COSMIC. Of interest, the L116R mutation in\n                  <jats:italic>Arh2<\/jats:italic>\n                  gene plays a critical role in aggressive tumorigenesis in nude mice, corresponding to human\n                  <jats:italic>ARH2<\/jats:italic>\n                  mutations in stomach adenocarcinoma. Both genders of\n                  <jats:italic>Arh2<\/jats:italic>\n                  -KO and -Het mice showed increased unexpectedly deaths and decreased survival rate during a 24-month observation, caused by tumor, inflammation, non-inflammation (e.g., cardiomegaly, dental dysplasia), and congenital diseases. Thus,\n                  <jats:italic>Arh2<\/jats:italic>\n                  plays a pivotal role in cardiac function, tumorigenesis, inflammation, and overall survival.\n                <\/jats:p>","DOI":"10.1101\/2023.02.07.527494","type":"posted-content","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T15:40:32Z","timestamp":1675784432000},"source":"Crossref","is-referenced-by-count":1,"title":["<i>ADP-ribose-acceptor hydrolase 2<\/i>\n                  (\n                  <i>Arh2<\/i>\n                  ) deficiency results in cardiac dysfunction, tumorigenesis, inflammation, and decreased survival"],"prefix":"10.64898","author":[{"given":"Jiro","family":"Kato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiko","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Ishiwata-Endo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunya","family":"Oka","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":"Audrey","family":"Noguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morteza","family":"Peiravi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J.","family":"Lizak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Medearis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In-Kwon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Moss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023020906550882000_2023.02.07.527494v1.1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/B978-0-12-152820-1.50010-9","article-title":"Mono (ADP-ribosyl)transferases and their effects on cellular metabolism","volume":"20","year":"1981","journal-title":"Curr Top Cell Regul"},{"key":"2023020906550882000_2023.02.07.527494v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3376"},{"key":"2023020906550882000_2023.02.07.527494v1.3","doi-asserted-by":"publisher","DOI":"10.3390\/cells4040569"},{"key":"2023020906550882000_2023.02.07.527494v1.4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.37.23617"},{"key":"2023020906550882000_2023.02.07.527494v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-010-0676-2"},{"issue":"18","key":"2023020906550882000_2023.02.07.527494v1.6","doi-asserted-by":"crossref","first-page":"8891","DOI":"10.1016\/S0021-9258(19)86783-2","article-title":"Substrate specificity and partial purification of a stereospecific NAD- and guanidine-dependent ADP-ribosyltransferase from avian erythrocytes","volume":"254","year":"1979","journal-title":"J Biol Chem"},{"key":"2023020906550882000_2023.02.07.527494v1.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.8.3621"},{"key":"2023020906550882000_2023.02.07.527494v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz120"},{"key":"2023020906550882000_2023.02.07.527494v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05588-5"},{"key":"2023020906550882000_2023.02.07.527494v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08859-x"},{"key":"2023020906550882000_2023.02.07.527494v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2521"},{"key":"2023020906550882000_2023.02.07.527494v1.12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.206771"},{"key":"2023020906550882000_2023.02.07.527494v1.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.17.5603"},{"key":"2023020906550882000_2023.02.07.527494v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)60277-X"},{"key":"2023020906550882000_2023.02.07.527494v1.15","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0054"},{"key":"2023020906550882000_2023.02.07.527494v1.16","doi-asserted-by":"crossref","unstructured":"Li T , Chen B , Wei C , Hou D , Qin P , Jing Z , et al. 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