{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T22:37:25Z","timestamp":1770503845740,"version":"3.49.0"},"reference-count":23,"publisher":"Proceedings of the National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,1,8]]},"abstract":"<jats:p>\n            p53 can adopt two forms\n            <jats:italic>in vitro<\/jats:italic>\n            , a latent\n form that binds naked DNA poorly and an active form that binds DNA\n well. Conversion of the latent form to the active form is\n thought to occur by an allosteric mechanism induced by phosphorylation\n and acetylation. Despite the large differences in affinity produced by\n regulatory modifications\n            <jats:italic>in vitro<\/jats:italic>\n            , mutation of putative\n regulatory sites has not produced correspondingly large effects on\n transcription of p53 target genes\n            <jats:italic>in vivo<\/jats:italic>\n            . To determine\n whether genotoxic stress regulates DNA binding by p53\n            <jats:italic>in\n vivo<\/jats:italic>\n            , we have performed quantitative chromatin\n immunoprecipitation (ChIP) assays on tumor and normal cell lines\n containing wild-type p53. ChIP recovers several hundredfold more p21\n and MDM2 promoter DNA from p53 wild-type than p53-null cells,\n indicating that the assay is specific for p53. Genotoxic stress induces\n much smaller increases in chromatin precipitation, which are matched by\n changes in the p53 protein level. Thus, in the experimental systems\n tested, allosteric regulation of DNA binding is not a major level of\n regulation of p53 activity. The p53 target genes tested can be divided\n into a group showing high promoter occupancy\n            <jats:italic>in vivo<\/jats:italic>\n            (p21, MDM2, and PUMA) and a group giving substantially weaker or\n background p53 binding (bax, AIP1, and PIG3). Neither group shows\n selective recruitment of p53 to the promoter in cells undergoing\n apoptosis, indicating that the decision to undergo\n apoptosis or cell cycle arrest depends on other changes in the\n cell.\n          <\/jats:p>","DOI":"10.1073\/pnas.012283399","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:36:44Z","timestamp":1027694204000},"page":"95-100","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":253,"title":["Chromatin immunoprecipitation analysis fails to support the latency model for regulation of p53 DNA binding activity\n            <i>in<\/i>\n            <i>vivo<\/i>"],"prefix":"10.1073","volume":"99","author":[{"given":"M. D.","family":"Kaeser","sequence":"first","affiliation":[{"name":"Oncogene Group, Swiss Institute for Experimental Cancer Research\r (ISREC), 1066 Epalinges, Switzerland"}]},{"given":"R. D.","family":"Iggo","sequence":"additional","affiliation":[{"name":"Oncogene Group, Swiss Institute for Experimental Cancer Research\r (ISREC), 1066 Epalinges, Switzerland"}]}],"member":"341","published-online":{"date-parts":[[2001,12,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.9.4952"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.19.2438"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00195-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202951"},{"key":"e_1_3_3_5_2","first-page":"789","volume":"10","author":"Fuchs B","year":"1995","unstructured":"B Fuchs, D O'Connor, L Fallis, K H Scheidtmann, X Lu Oncogene 10, 789\u2013793 (1995).","journal-title":"Oncogene"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202480"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.3.1751"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.24.3471"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00283-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.19.2490"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.10.3375-3386.2001"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5393.1497"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(92)90122-A"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.16.4424"},{"key":"e_1_3_3_15_2","first-page":"2523","volume":"9","author":"Picksley S M","year":"1994","unstructured":"S M Picksley, B Vojtesek, A Sparks, D P Lane Oncogene 9, 2523\u20132529 (1994).","journal-title":"Oncogene"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06874.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8023157"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.13777"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6863"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.12b.2556"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401691"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.5.2768"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.859201"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.012283399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T12:51:23Z","timestamp":1649767883000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.012283399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,12,26]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,1,8]]}},"alternative-id":["10.1073\/pnas.012283399"],"URL":"https:\/\/doi.org\/10.1073\/pnas.012283399","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,12,26]]},"assertion":[{"value":"2001-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}