{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:09:16Z","timestamp":1791994156193,"version":"4.4.0"},"reference-count":25,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5647","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,11,7]]},"abstract":"<jats:p>\n                    Apoptosis provoked by DNA damage requires the p53 tumor suppressor, but which of the many p53-regulated genes are required has remained unknown. Two genes induced by this transcription factor,\n                    <jats:italic>noxa<\/jats:italic>\n                    and\n                    <jats:italic>puma<\/jats:italic>\n                    (\n                    <jats:italic>bbc3<\/jats:italic>\n                    ), stand out, because they encode BH3-only proteins, proapoptotic members of the Bcl-2 family required to initiate apoptosis. In mice with either\n                    <jats:italic>noxa<\/jats:italic>\n                    or\n                    <jats:italic>puma<\/jats:italic>\n                    disrupted, we observed decreased DNA damage\u2013induced apoptosis in fibroblasts, although only loss of Puma protected lymphocytes from cell death. Puma deficiency also protected cells against diverse p53-independent cytotoxic insults, including cytokine deprivation and exposure to glucocorticoids, the kinase inhibitor staurosporine, or phorbol ester. Hence, Puma and Noxa are critical mediators of the apoptotic responses induced by p53 and other agents.\n                  <\/jats:p>","DOI":"10.1126\/science.1090072","type":"journal-article","created":{"date-parts":[[2003,9,22]],"date-time":"2003-09-22T21:33:53Z","timestamp":1064266433000},"page":"1036-1038","source":"Crossref","is-referenced-by-count":1157,"title":["p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa"],"prefix":"10.1126","volume":"302","author":[{"given":"Andreas","family":"Villunger","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia."},{"name":"Institute for Pathophysiology, University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa M.","family":"Michalak","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia."},{"name":"Institute for Pathophysiology, University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Coultas","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia."},{"name":"Institute for Pathophysiology, University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Mu\u0308llauer","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia."},{"name":"Institute for Pathophysiology, University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu\u0308nther","family":"Bo\u0308ck","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia."},{"name":"Institute for Pathophysiology, University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Ausserlechner","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia."},{"name":"Institute for Pathophysiology, University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry M.","family":"Adams","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia."},{"name":"Institute for Pathophysiology, University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Strasser","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia."},{"name":"Institute for Pathophysiology, University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35037717"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc864"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5468.1053"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00214-3"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00213-1"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.201208798"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5445.1735"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00136-2"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc883"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90573-H"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90362-3"},{"key":"e_1_3_1_13_2","unstructured":"A. Villunger E. M. Michalak J. M. Adams A. Strasser unpublished observations."},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/362847a0"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/362849a0"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90719-7"},{"key":"e_1_3_1_17_2","first-page":"2","volume":"2","year":"2003","unstructured":"T. Shibueet al., Genes Dev.2, 2 (2003).","journal-title":"Genes Dev."},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2627984100"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401180"},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.4049\/jimmunol.139.10.3199","volume":"139","year":"1987","unstructured":"K. S. Sellins, J. J. Cohen, J. Immunol.139, 3199 (1987).","journal-title":"J. Immunol."},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.18.4967"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/79152"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90201-1"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/415922a"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.14943"},{"key":"e_1_3_1_26_2","unstructured":"We thank E. Stanley W. Alexander and M. Santamaria for advice on gene targeting; M. Pellegrini for help with retrovirus infection; T. Taniguchi for communicating results on noxa \u2013\/\u2013 mice ( 16 ); G. Baier T. Chittenden and B. Vogelstein for reagents; K. Rossi for mouse genotyping and animal care; S. Lobenwein for help with viral transformations; F. Battye C. Tarlinton V. Lapatis and C. Clark for cell sorting; and S. Cory G. Wick A. Harris D. Vaux D. Huang H. Puthalakath P. Bouillet and L. O'Reilly for insightful discussions. Supported by fellowships and grants from the National Health and Medical Research Council (Canberra); the Dr. Josef Steiner Cancer Research Foundation (Bern); the Leukemia and Lymphoma Society (Specialized Center of Research); the NIH; the Anti-Cancer Council of Victoria; the Austrian Ministry for Education Science and Culture (GENAU-Child); and the Austrian Science Fund."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1090072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:12:47Z","timestamp":1704838367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1090072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,7]]},"references-count":25,"journal-issue":{"issue":"5647","published-print":{"date-parts":[[2003,11,7]]}},"alternative-id":["10.1126\/science.1090072"],"URL":"https:\/\/doi.org\/10.1126\/science.1090072","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1015889.200721","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1015889.199057","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11,7]]}}}