{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:41:15Z","timestamp":1781106075781,"version":"3.54.1"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,4,26]]},"abstract":"<jats:p>\n                    Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2\u2013regulated apoptosis pathway in\n                    <jats:italic>Schistosoma japonicum<\/jats:italic>\n                    and\n                    <jats:italic>S. mansoni.<\/jats:italic>\n                    Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2\u2013like molecules, and Bax\/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with \u201cBH3 mimetic\u201d drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1100652108","type":"journal-article","created":{"date-parts":[[2011,3,28]],"date-time":"2011-03-28T22:34:26Z","timestamp":1301351666000},"page":"6999-7003","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":50,"title":["Discovery and molecular characterization of a Bcl-2\u2013regulated cell death pathway in schistosomes"],"prefix":"10.1073","volume":"108","author":[{"given":"Erinna F.","family":"Lee","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; and"},{"name":"Departments of bMedical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver B.","family":"Clarke","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; and"},{"name":"Departments of bMedical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Evangelista","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; and"},{"name":"Departments of bMedical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiping","family":"Feng","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; and"},{"name":"Departments of bMedical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence P.","family":"Speed","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; and"},{"name":"Departments of bMedical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elissaveta B.","family":"Tchoubrieva","sequence":"additional","affiliation":[{"name":"Veterinary Science, University of Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Strasser","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; and"},{"name":"Departments of bMedical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd H.","family":"Kalinna","sequence":"additional","affiliation":[{"name":"Veterinary Science, University of Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Colman","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; and"},{"name":"Departments of bMedical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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