{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:28:31Z","timestamp":1781108911003,"version":"3.54.1"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,6,22]]},"abstract":"<jats:p>\n                    The p53 tumor suppressor regulates diverse antiproliferative processes such that cells acquiring\n                    <jats:italic>p53<\/jats:italic>\n                    mutations have impaired cell-cycle checkpoints, senescence, apoptosis, and genomic stability. Here, we use stable RNA interference to examine the role of PUMA, a p53 target gene and proapoptotic member of the Bcl2 family, in p53-mediated tumor suppression.\n                    <jats:italic>PUMA<\/jats:italic>\n                    short hairpin RNAs (shRNAs) efficiently suppressed\n                    <jats:italic>PUMA<\/jats:italic>\n                    expression and p53-dependent apoptosis but did not impair nonapoptotic functions of p53. Like\n                    <jats:italic>p53<\/jats:italic>\n                    shRNAs,\n                    <jats:italic>PUMA<\/jats:italic>\n                    shRNAs promoted oncogenic transformation of primary murine fibroblasts by the\n                    <jats:italic>E1A\/ras<\/jats:italic>\n                    oncogene combination and dramatically accelerated\n                    <jats:italic>myc<\/jats:italic>\n                    -induced lymphomagenesis without disrupting p53-dependent cell-cycle arrest. However, the ability of PUMA to execute p53 tumor suppressor functions was variable because, in contrast to\n                    <jats:italic>p53<\/jats:italic>\n                    shRNAs,\n                    <jats:italic>PUMA<\/jats:italic>\n                    shRNAs were unable to cooperate with oncogenic\n                    <jats:italic>ras<\/jats:italic>\n                    in transformation. These results demonstrate that the p53 effector functions involved in tumor suppression are context dependent and, in some settings, depend heavily on the expression of a single proapoptotic effector. Additionally, they demonstrate the utility of RNA interference for evaluating putative tumor suppressor genes\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.0403286101","type":"journal-article","created":{"date-parts":[[2004,6,10]],"date-time":"2004-06-10T20:13:45Z","timestamp":1086898425000},"page":"9333-9338","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":152,"title":["Suppression of tumorigenesis by the p53 target PUMA"],"prefix":"10.1073","volume":"101","author":[{"given":"Michael T.","family":"Hemann","sequence":"first","affiliation":[{"name":"Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724; and Genetics Program, Stony Brook University, Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack T.","family":"Zilfou","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724; and Genetics Program, Stony Brook University, Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724; and Genetics Program, Stony Brook University, Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren J.","family":"Burgess","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724; and Genetics Program, Stony Brook University, Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Hannon","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724; and Genetics Program, Stony Brook University, Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott W.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724; and Genetics Program, Stony Brook University, Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,6,10]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35042675"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.20.2658"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/385637a0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.897601"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207116"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00047-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/356215a0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90362-3"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90361-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1282"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00213-1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00214-3"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2627984100"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090072"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00244-7"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1091"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00734-1"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.981002"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2026"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81902-9"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.12.3974-3985.2001"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.19.3008"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90719-7"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90593-2"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/312649a0"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.4.546"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/318533a0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.20.2670"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428190009060325"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199509000-00002"},{"key":"e_1_3_2_31_2","first-page":"1358","volume":"7","year":"2001","unstructured":"Mora, J., Cheung, N. K., Chen, L., Qin, J. & Gerald, W. (2001) Clin. Cancer Res. 7, 1358-1361.11350906","journal-title":"Clin. Cancer Res."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.4.535"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.16.7742"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0403286101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T09:43:58Z","timestamp":1649756638000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0403286101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6,10]]},"references-count":33,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2004,6,22]]}},"alternative-id":["10.1073\/pnas.0403286101"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0403286101","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6,10]]},"assertion":[{"value":"2004-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}