{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:49:55Z","timestamp":1775591395856,"version":"3.50.1"},"reference-count":18,"publisher":"Proceedings of the National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,11,11]]},"abstract":"<jats:p>\n            We designed a series of nine-residue peptides that bound to a defined site on the tumor suppressor p53 and stabilized it against denaturation. To test whether the peptides could act as chaperones and rescue the tumor-suppressing function of oncogenic mutants of p53 in living cells, we treated human tumor cells with the fluorescein-labeled peptide Fl-CDB3 (fluorescent derivative of CDB3). Before treatment, the mutant p53 in the cell was predominantly denatured. Fl-CDB3 was taken up into the cytoplasm and nucleus and induced a substantial up-regulation of wild-type p53 protein and representative mutants. The mutants, His-273 and His-175 p53, adopted the active conformation, with a dramatic decrease in the fraction of denatured protein. In all cases, there was p53-dependent induction of expression of the p53 target genes\n            <jats:italic>mdm2, gadd45<\/jats:italic>\n            , and\n            <jats:italic>p21<\/jats:italic>\n            , accompanied by p53-dependent partial restoration of apoptosis. Fl-CDB3 sensitized cancer cells that carried wild-type p53 to p53-dependent \u03b3-radiation-induced apoptosis. Although Fl-CDB3 did not elicit a full biological response, it did bind to and rescue p53 in cells and so can serve as a lead for the development of novel drugs for anticancer therapy.\n          <\/jats:p>","DOI":"10.1073\/pnas.1835733100","type":"journal-article","created":{"date-parts":[[2003,11,16]],"date-time":"2003-11-16T20:42:47Z","timestamp":1069015367000},"page":"13303-13307","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":118,"title":["Rescue of mutants of the tumor suppressor p53 in cancer cells by a designed peptide"],"prefix":"10.1073","volume":"100","author":[{"given":"Natalia","family":"Issaeva","sequence":"first","affiliation":[{"name":"Department of Oncology-Pathology, Cancer Center Karolinska, R8:00, Karolinska Institutet, Karolinska Hospital, SE-171 76 Stockholm, Sweden; Medical Research Council Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Assaf","family":"Friedler","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Cancer Center Karolinska, R8:00, Karolinska Institutet, Karolinska Hospital, SE-171 76 Stockholm, Sweden; Medical Research Council Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Przemyslaw","family":"Bozko","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Cancer Center Karolinska, R8:00, Karolinska Institutet, Karolinska Hospital, SE-171 76 Stockholm, Sweden; Medical Research Council Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klas G.","family":"Wiman","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Cancer Center Karolinska, R8:00, Karolinska Institutet, Karolinska Hospital, SE-171 76 Stockholm, Sweden; Medical Research Council Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan R.","family":"Fersht","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Cancer Center Karolinska, R8:00, Karolinska Institutet, Karolinska Hospital, SE-171 76 Stockholm, Sweden; Medical Research Council Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina","family":"Selivanova","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Cancer Center Karolinska, R8:00, Karolinska Institutet, Karolinska Hospital, SE-171 76 Stockholm, Sweden; Medical Research Council Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2003,10,31]]},"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":"10.1126\/science.8023157"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203434"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14338"},{"key":"e_1_3_2_5_2","first-page":"47","volume":"1602","year":"2002","unstructured":"Vousden, K. 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