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These tumors continue to express wild-type beclin 1 mRNA and protein, establishing that beclin 1 is a haploinsufficient tumor suppressor gene. Beclin 1\n                    <jats:sup>-\/-<\/jats:sup>\n                    embryonic stem cells have a severely altered autophagic response, whereas their apoptotic response to serum withdrawal or UV light is normal. These results demonstrate that beclin 1 is a critical component of mammalian autophagy and establish a role for autophagy in tumor suppression. They both provide a biological explanation for recent evidence implicating beclin 1 in human cancer and suggest that mutations in other genes operating in this pathway may contribute to tumor formation through deregulation of autophagy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2436255100","type":"journal-article","created":{"date-parts":[[2003,12,9]],"date-time":"2003-12-09T13:17:48Z","timestamp":1070975868000},"page":"15077-15082","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1765,"title":["Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor"],"prefix":"10.1073","volume":"100","author":[{"given":"Zhenyu","family":"Yue","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, Howard Hughes Medical Institute, and Gene Targeting Facility, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Pharmacology, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854; and Pediatrics Department, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08903"}]},{"given":"Shengkan","family":"Jin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Howard Hughes Medical Institute, and Gene Targeting Facility, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Pharmacology, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854; and Pediatrics Department, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08903"}]},{"given":"Chingwen","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Howard Hughes Medical Institute, and Gene Targeting Facility, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Pharmacology, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854; and Pediatrics Department, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08903"}]},{"given":"Arnold J.","family":"Levine","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Howard Hughes Medical Institute, and Gene Targeting Facility, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Pharmacology, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854; and Pediatrics Department, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08903"}]},{"given":"Nathaniel","family":"Heintz","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Howard Hughes Medical Institute, and Gene Targeting Facility, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Pharmacology, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854; and Pediatrics Department, University of Medicine and Dentistry of New Jersey\u2013Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08903"}]}],"member":"341","published-online":{"date-parts":[[2003,12]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1717"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35056522"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(02)00343-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400852"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1999.0780"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/45257"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.11.8586-8596.1998"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5851"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00861-9"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199811)213:3<293::AID-AJA6>3.0.CO;2-D"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.143.2.547"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.152.4.657"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/35069004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/1235"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/86912"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf413"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.18.4967"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0290684"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","unstructured":"Rossant J. & Cross J. 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