{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:03:06Z","timestamp":1791424986140,"version":"4.3.3"},"reference-count":47,"publisher":"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":[[2005,4,12]]},"abstract":"<jats:p>\n                    NAD(P)H:quinone oxidoreductase 1 (NQO1) regulates the stability of the tumor suppressor WT p53. NQO1 binds and stabilizes WT p53, whereas NQO1 inhibitors including dicoumarol and various other coumarins and flavones induce ubiquitin-independent proteasomal p53 degradation and thus inhibit p53-induced apoptosis. Here, we show that curcumin, a natural phenolic compound found in the spice turmeric, induced ubiquitin-independent degradation of WT p53 and inhibited p53-induced apoptosis in normal thymocytes and myeloid leukemic cells. Like dicoumarol, curcumin inhibited the activity of recombinant NQO1\n                    <jats:italic>in vitro<\/jats:italic>\n                    , inhibited the activity of endogenous cellular NQO1\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and dissociated NQO1-WT p53 complexes. Neither dicoumarol nor curcumin dissociated the complexes of NQO1 and the human cancer hot-spot p53 R273H mutant and therefore did not induce degradation of this mutant. NQO1 knockdown by small-interfering RNA induced degradation of both WT p53 and the p53 R273H mutant. The results indicate that curcumin induces p53 degradation and inhibits p53-induced apoptosis by an NQO1-dependent pathway.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0501828102","type":"journal-article","created":{"date-parts":[[2005,4,4]],"date-time":"2005-04-04T20:31:36Z","timestamp":1112646696000},"page":"5535-5540","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":135,"title":["Inhibition of NAD(P)H:quinone oxidoreductase 1 activity and induction of p53 degradation by the natural phenolic compound curcumin"],"prefix":"10.1073","volume":"102","author":[{"given":"Peter","family":"Tsvetkov","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gad","family":"Asher","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Reiss","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosef","family":"Shaul","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Sachs","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Lotem","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,4,4]]},"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":"10.1016\/0092-8674(92)90421-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.6.13.1397838"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81871-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/352345a0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.4.1092.1092"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/362847a0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/362849a0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1009614723237"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205319"},{"key":"e_1_3_2_11_2","first-page":"3551","volume":"22","year":"1994","unstructured":"Hollstein, M., Rice, K., Greenblatt, M. 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