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Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor,\n                    <jats:italic>Pseudomonas exotoxin<\/jats:italic>\n                    fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation\n                    <jats:italic>in vivo<\/jats:italic>\n                    , as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen\n                    <jats:italic>in vivo<\/jats:italic>\n                    , showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0236849100","type":"journal-article","created":{"date-parts":[[2003,1,21]],"date-time":"2003-01-21T17:51:47Z","timestamp":1043171507000},"page":"657-662","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":102,"title":["Potent antitumor activity of a urokinase-activated engineered anthrax toxin"],"prefix":"10.1073","volume":"100","author":[{"given":"Shihui","family":"Liu","sequence":"first","affiliation":[{"name":"Oral Infection and Immunity Branch and Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Aaronson","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch and Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Mitola","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch and Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Leppla","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch and Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Bugge","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch and Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,1,13]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19970703)72:1<1::AID-IJC1>3.0.CO;2-Z"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1999.tb01534.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000180050497"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0396-287"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.20.4481"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/13459"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00268a014"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.28.16886"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.5899"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.140.1.233"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.11.3839"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-29-3-517"},{"key":"e_1_3_3_13_2","first-page":"543","volume-title":"Bacterial Toxins and Virulence Factors in Disease. 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