{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:12:26Z","timestamp":1785420746369,"version":"3.56.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"25","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA47296"],"award-info":[{"award-number":["R01CA47296"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R50CA251703"],"award-info":[{"award-number":["R50CA251703"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                    tumor suppressor encodes a transcription factor that regulates the expression of hundreds of target genes. Previous mouse studies have identified a conserved p53-dependent transcriptional signature that includes\n                    <jats:italic toggle=\"yes\">Cdkn1A (p21)<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Gtse1<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">G2 and S-phase expressed 1<\/jats:italic>\n                    ), and\n                    <jats:italic toggle=\"yes\">Eda2r<\/jats:italic>\n                    . In this study, we investigated the physiological roles of these three genes, along with\n                    <jats:italic toggle=\"yes\">Bbc3<\/jats:italic>\n                    (Puma), a p53 target involved in apoptosis, as effectors of p53 activity. We generated alleles of\n                    <jats:italic toggle=\"yes\">Gtse1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Eda2r<\/jats:italic>\n                    . In contrast to previously reported\n                    <jats:italic toggle=\"yes\">Cdkn1A-null<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Bbc3-null<\/jats:italic>\n                    mice which do not exhibit any overt phenotypes, mice expressing N-terminal deletions of\n                    <jats:italic toggle=\"yes\">Gtse1<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Gtse1\u03947<\/jats:italic>\n                    ) and\n                    <jats:italic toggle=\"yes\">Eda2r<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Eda2r\u039411<\/jats:italic>\n                    ) displayed defects in spermatogenesis and liver abnormalities, respectively. We crossed these mice to an\n                    <jats:italic toggle=\"yes\">Mdm2<\/jats:italic>\n                    -deletion model that constitutively activates p53 resulting in multiple phenotypes and lethality. Notably, loss of\n                    <jats:italic toggle=\"yes\">p21<\/jats:italic>\n                    rescued the lethality associated with constitutive p53 activation in vivo, whereas the\n                    <jats:italic toggle=\"yes\">Gtse1\u03947<\/jats:italic>\n                    mutant partially rescued this effect; no rescue was observed with\n                    <jats:italic toggle=\"yes\">Eda2r\u039411<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">Bbc3<\/jats:italic>\n                    loss. These findings indicate that cell cycle regulators, rather than apoptosis-related genes, are the main drivers of sustained p53-induced gastrointestinal defects and lethality.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2536303123","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:16:51Z","timestamp":1781626611000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["The physiological relevance of downstream effectors of p53 activity"],"prefix":"10.1073","volume":"123","author":[{"given":"Vinod","family":"Pant","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics, The University of Texas MD Anderson Cancer Center","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney M.","family":"Moyer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics, The University of Texas MD Anderson Cancer Center","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitheera","family":"V","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics, The University of Texas MD Anderson Cancer Center","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda R.","family":"Wasylishen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics, The University of Texas MD Anderson Cancer Center","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshita","family":"Mirani","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics, The University of Texas MD Anderson Cancer Center","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Fowlkes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8985-4886","authenticated-orcid":false,"given":"Guillermina","family":"Lozano","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics, The University of Texas MD Anderson Cancer Center","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.12.011"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-023-01123-2"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.037"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.89"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt504"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02200"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-14-0177"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.01.020"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.212282.112"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.111"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.227249.113"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1909550116"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1667\/RR2545.1"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.05.017"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008474117"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112216"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44319-025-00375-y"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.17.5015"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00260-2"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302902200"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051259"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","unstructured":"C. Tanikawa XEDAR as a putative colorectal tumor suppressor that mediates p53-regulated anoikis pathway. Oncogene 28 3081\u20133092 (2009).","DOI":"10.1038\/onc.2009.154"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.04.058"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.4.1608-1613.2004"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70282"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90500-P"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00213-1"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90039-X"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00244-7"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.008672"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.07.015"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4368"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.10.010"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.09.009"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00555-06"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.9.2.1"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000034996"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0706-9"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44957"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1282"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-1421"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjz063"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10066"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2536303123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:16:54Z","timestamp":1781626614000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2536303123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":43,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2026,6,23]]}},"alternative-id":["10.1073\/pnas.2536303123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2536303123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"assertion":[{"value":"2025-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2536303123"}}