{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T18:39:37Z","timestamp":1778092777067,"version":"3.51.4"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>p53 is a key tumor suppressor mutated in half of human cancers. In recent years, p53 was shown to regulate a wide variety of functions. From the transcriptome analysis of 24 tissues of irradiated mice, we identified 553 genes markedly induced by p53. Gene Ontology (GO) enrichment analysis found that the most associated biological process was innate immunity. 16S rRNA\u2010seq analysis revealed that <jats:italic>Akkermansia<\/jats:italic>, which has anti\u2010inflammatory properties and is involved in the regulation of intestinal barrier integrity, was decreased in p53\u2010knockout (<jats:italic>p53<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) mice after radiation. <jats:italic>p53<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice were susceptible to radiation\u2010induced GI toxicity and had a significantly shorter survival time than p53\u2010wild\u2010type (<jats:italic>p53<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup>) mice following radiation. However, administration of antibiotics resulted in a significant improvement in survival and protection against GI toxicity. <jats:italic>Mbl2<\/jats:italic> and <jats:italic>Lcn2<\/jats:italic>, which have antimicrobial activity, were identified to be directly transactivated by p53 and secreted by liver into the circulatory system. We also found the expression of <jats:italic>MBL2<\/jats:italic> and <jats:italic>LCN2<\/jats:italic> was decreased in liver cancer tissues with p53 mutations compared with those without p53 mutations. These results indicate that p53 is involved in shaping the gut microbiome through its downstream targets related to the innate immune system, thus protecting the intestinal barrier.<\/jats:p>","DOI":"10.1111\/cas.15991","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T06:10:55Z","timestamp":1701756655000},"page":"184-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Regulation of the innate immune response and gut microbiome by p53"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2132-6726","authenticated-orcid":false,"given":"Amy Hui Ping","family":"Khor","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Minato City, Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Koguchi","sequence":"additional","affiliation":[{"name":"Department of Urology Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Minato City, Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Kakuta","sequence":"additional","affiliation":[{"name":"Department of Integrated Analytics, M&amp;D Data Science Center Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine University of Tsukuba  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruimeng","family":"Wen","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Minato City, Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoji","family":"Sagiya","sequence":"additional","affiliation":[{"name":"Laboratory of Genome Technology, Human Genome Center, The Institute of Medical Science The University of Tokyo  Minato City, Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiya","family":"Imoto","sequence":"additional","affiliation":[{"name":"Division of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science The University of Tokyo  Minato City, Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1807-772X","authenticated-orcid":false,"given":"Hidewaki","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Laboratory for Cancer Genomics RIKEN Center for Integrative Medical Sciences  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Minato City, Tokyo Japan"},{"name":"Laboratory of Genome Technology, Human Genome Center, The Institute of Medical Science The University of Tokyo  Minato City, Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chizu","family":"Tanikawa","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Minato City, Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.502"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.08.028"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.12.011"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.05.017"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.002"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0126-x"},{"key":"e_1_2_12_8_1","first-page":"3313","article-title":"Enhanced proliferative potential in culture of cells from p53\u2010deficient mice","volume":"8","author":"Tsukada T","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017996"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.04.008"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-6-r60"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219451110"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.04050-14"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2015.00084"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02994-21"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-021-02638-x"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0157-3"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1909550116"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1166202"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-11-0052"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207494"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0492-45"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab996"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1113"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37922-8"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0992-50"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2005.06.033"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu666"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290417"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.4124"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.688-693.2000"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.100"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/6738286"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.12.6945"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.3.1462"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1349784"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.759183"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2017.01.003"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2002.110611.x"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27447"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510847103"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050052"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.05.051"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2016.03.007"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2015.06.011"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2020.03.008"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.03.007"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02427-7"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.281"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2012.110"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071108"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.282"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00631-9"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-320105"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031105"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.11.014"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.15991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T04:26:10Z","timestamp":1717388770000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.15991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,4]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/cas.15991"],"URL":"https:\/\/doi.org\/10.1111\/cas.15991","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,4]]},"assertion":[{"value":"2023-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}