{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:52:30Z","timestamp":1774486350284,"version":"3.50.1"},"reference-count":40,"publisher":"Proceedings of the National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,7,17]]},"abstract":"<jats:p>\n                    The inhibitor of apoptosis (IAP) family of anti-apoptotic proteins regulate programmed cell death and\/or apoptosis. One such protein, X-linked IAP (XIAP), inhibits the activity of the cell death proteases, caspase-3, -7, and -9. In this study, using constitutively active mutants of caspase-3, we found that XIAP promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. The XIAP mutants, which cannot interact with caspase-3, had little or no activity of promoting the degradation of caspase-3. RING finger mutants of XIAP also could not promote the degradation of caspase-3. A proteasome inhibitor suppressed the degradation of caspase-3 by XIAP, suggesting the involvement of a ubiquitin-proteasome pathway in the degradation. An\n                    <jats:italic>in vitro<\/jats:italic>\n                    ubiquitination assay revealed that XIAP acts as a ubiquitin-protein ligase for caspase-3. Caspase-3 was ubiquitinated in the presence of XIAP in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. Finally, the RING finger mutants of XIAP were less effective than wild-type XIAP at preventing apoptosis induced by overexpression of either active-form caspase-3 or Fas. These results demonstrate that the ubiquitin-protein ligase activity of XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.\n                  <\/jats:p>","DOI":"10.1073\/pnas.161506698","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"8662-8667","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":514,"title":["Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death"],"prefix":"10.1073","volume":"98","author":[{"given":"Yasuyuki","family":"Suzuki","sequence":"first","affiliation":[{"name":"Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Wako City, Saitama 351-0198, Japan"}]},{"given":"Yui","family":"Nakabayashi","sequence":"additional","affiliation":[{"name":"Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Wako City, Saitama 351-0198, Japan"}]},{"given":"Ryosuke","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Wako City, Saitama 351-0198, Japan"}]}],"member":"341","published-online":{"date-parts":[[2001,7,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81873-5"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7878464"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1312"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.11.1551"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(99)01609-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.3.239"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/40901"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.23.6914"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.8.2215"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.14.7787"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.19.5242"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006226200"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3429"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00287-6"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00077-5"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.24.7151"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/387299a0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.8945"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.20.2701"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.1.724"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5467.874"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)61427-4"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10107"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/44617"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11364"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.32.22151"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80231-2"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.12.1775"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00274-4"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/35068604"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81974-1"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.4.598"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90150-7"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.51.33915"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.14.8.5212-5222.1994"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6015"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/154.2.669"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80887-9"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.22.6462"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.22.6455"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.161506698","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:01:09Z","timestamp":1649811669000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.161506698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,7,10]]},"references-count":40,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2001,7,17]]}},"alternative-id":["10.1073\/pnas.161506698"],"URL":"https:\/\/doi.org\/10.1073\/pnas.161506698","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1000296.7501","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,7,10]]},"assertion":[{"value":"2000-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-07-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}