{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:55:40Z","timestamp":1791042940839,"version":"4.1.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,2,15]]},"abstract":"<jats:p>\n                    DNA damage induced by ionizing radiation (IR) activates p53, leading to the regulation of downstream pathways that control cell-cycle progression and apoptosis. However, the mechanisms for the IR-induced p53 activation and the differential activation of pathways downstream of p53 are unclear. Here we provide evidence that the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) serves as an upstream effector for p53 activation in response to IR, linking DNA damage to apoptosis.\n                    <jats:italic>DNA-PKcs<\/jats:italic>\n                    knockout (\n                    <jats:italic>DNA-PKcs<\/jats:italic>\n                    \u2212\/\u2212) mice were exposed to whole-body IR, and the cell-cycle and apoptotic responses were examined in their thymuses. Our data show that IR induction of apoptosis and Bax expression, both mediated via p53, was significantly suppressed in the thymocytes of\n                    <jats:italic>DNA-PKcs<\/jats:italic>\n                    \u2212\/\u2212 mice. In contrast, IR-induced cell-cycle arrest and p21 expression were normal. Thus, DNA-PKcs deficiency selectively disrupts p53-dependent apoptosis but not cell-cycle arrest. We also confirmed previous findings that p21 induction was attenuated and cell-cycle arrest was defective in the thymoctyes of whole body-irradiated\n                    <jats:italic>Atm<\/jats:italic>\n                    \u2212\/\u2212 mice, but the apoptotic response was unperturbed. Taken together, our results support a model in which the upstream effectors DNA-PKcs and Atm selectively activate p53 to differentially regulate cell-cycle and apoptotic responses. Whereas Atm selects for cell-cycle arrest but not apoptosis, DNA-PKcs selects for apoptosis but not cell-cycle arrest.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.4.1584","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"1584-1588","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":117,"title":["The catalytic subunit of DNA-dependent protein kinase selectively regulates p53-dependent apoptosis but not cell-cycle arrest"],"prefix":"10.1073","volume":"97","author":[{"given":"Sa","family":"Wang","sequence":"first","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Guo","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghai","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Li","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Cordon-Cardo","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Kurimasa","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Chen","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi","family":"Fuks","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Clifton","family":"Ling","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria C.","family":"Li","sequence":"additional","affiliation":[{"name":"Departments of Medical Physics, Radiation Oncology, and Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,2,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.9.1054"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81871-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-453"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/29343"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.24.3471"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199901)187:1<127::AID-PATH251>3.0.CO;2-T"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.8.916"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(93)90144-C"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2438"},{"key":"e_1_3_3_10_2","first-page":"2940","volume":"56","author":"Huang L C","year":"1996","unstructured":"L C Huang, K C Clarkin, G M Wahl Cancer Res 56, 2940\u20132944 (1996).","journal-title":"Cancer Res"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.16.2038"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/17.12.2537"},{"key":"e_1_3_3_13_2","first-page":"68","volume":"57","author":"Rathmell W K","year":"1997","unstructured":"W K Rathmell, W K Kaufmann, J C Hurt, L L Byrd, G Chu Cancer Res 57, 68\u201374 (1997).","journal-title":"Cancer Res"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.4.1403"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.24.17139"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/362847a0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80091-4"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00002-6"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.4.3095"},{"key":"e_1_3_3_20_2","first-page":"62","volume":"1","author":"Fuks Z","year":"1995","unstructured":"Z Fuks, A Alfieri, A Haimovitz-Friedman, A Seddon, C Cordon-Cardo Cancer J 1, 62\u201372 (1995).","journal-title":"Cancer J"},{"key":"e_1_3_3_21_2","volume-title":"Antibodies: A Laboratory Manual","author":"Harlow E","year":"1988","unstructured":"E Harlow, D Lane Antibodies: A Laboratory Manual (Cold Spring Harbor Lab. Press, Plainview, NY, 1988)."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.6.921"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/382551a0"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80086-0"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90039-X"},{"key":"e_1_3_3_26_2","first-page":"6304","volume":"51","author":"Kastan M B","year":"1991","unstructured":"M B Kastan, O Onyekwere, D Sidransky, B Vogelstein, R W Craig Cancer Res 51, 6304\u20136311 (1991).","journal-title":"Cancer Res"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/377552a0"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90500-P"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90499-G"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90513-8"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.19.2438"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.7.1815"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.10.12.6472-6481.1990"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1674"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1677"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/3882"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.2.152"},{"key":"e_1_3_3_38_2","first-page":"3543","volume":"59","author":"Araki R","year":"1999","unstructured":"R Araki, R Fukumura, A Fujimori, Y Taya, Y Shiloh, A Kurimasa, S Burma, G C Li, D J Chen, K Sato, et al. Cancer Res 59, 3543\u20133546 (1999).","journal-title":"Cancer Res"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/21913"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.97.4.1584","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:11:45Z","timestamp":1649869905000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.97.4.1584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,2,15]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2000,2,15]]}},"alternative-id":["10.1073\/pnas.97.4.1584"],"URL":"https:\/\/doi.org\/10.1073\/pnas.97.4.1584","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,2,15]]},"assertion":[{"value":"1999-09-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-11-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-02-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}