{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:28:39Z","timestamp":1791253719069,"version":"4.1.0"},"reference-count":74,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,3,9]]},"abstract":"<jats:p>\n                    The mammalian F-box protein Fbw7 and its\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    counterpart Sel-10 have been implicated in the ubiquitin-mediated turnover of cyclin E as well as the Notch\/Lin-12 family of transcriptional activators. Both unregulated Notch and cyclin E promote tumorigenesis, and inactivating mutations in human\n                    <jats:italic>Fbw7<\/jats:italic>\n                    suggest that it may be a tumor suppressor. To generate an\n                    <jats:italic>in vivo<\/jats:italic>\n                    system to assess the consequences of such unregulated signaling, we generated mice deficient for\n                    <jats:italic>Fbw7. Fbw7<\/jats:italic>\n                    -null mice die around 10.5 days post coitus because of a combination of deficiencies in hematopoietic and vascular development and heart chamber maturation. The absence of Fbw7 results in elevated levels of cyclin E, concurrent with inappropriate DNA replication in placental giant trophoblast cells. Moreover, the levels of both Notch 1 and Notch 4 intracellular domains were elevated, leading to stimulation of downstream transcriptional pathways involving Hes1, Herp1, and Herp2. These data suggest essential functions for Fbw7 in controlling cyclin E and Notch signaling pathways in the mouse.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0307875101","type":"journal-article","created":{"date-parts":[[2004,3,11]],"date-time":"2004-03-11T15:20:15Z","timestamp":1079018415000},"page":"3338-3345","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":217,"title":["Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein"],"prefix":"10.1073","volume":"101","author":[{"given":"Michael T.","family":"Tetzlaff","sequence":"first","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry, Departments of Human and Molecular Genetics, Molecular and Cellular Biology, Molecular Physiology and Biophysics, and Pathology, Texas Children's Hospital, Howard Hughes Medical Institute, and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yu","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry, Departments of Human and Molecular Genetics, Molecular and Cellular Biology, Molecular Physiology and Biophysics, and Pathology, Texas Children's Hospital, Howard Hughes Medical Institute, and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamie","family":"Li","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry, Departments of Human and Molecular Genetics, Molecular and Cellular Biology, Molecular Physiology and Biophysics, and Pathology, Texas Children's Hospital, Howard Hughes Medical Institute, and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pumin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry, Departments of Human and Molecular Genetics, Molecular and Cellular Biology, Molecular Physiology and Biophysics, and Pathology, Texas Children's Hospital, Howard Hughes Medical Institute, and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Finegold","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry, Departments of Human and Molecular Genetics, Molecular and Cellular Biology, Molecular Physiology and Biophysics, and Pathology, Texas Children's Hospital, Howard Hughes Medical Institute, and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Mahon","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry, Departments of Human and Molecular Genetics, Molecular and Cellular Biology, Molecular Physiology and Biophysics, and Pathology, Texas Children's Hospital, Howard Hughes Medical Institute, and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Wade","family":"Harper","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry, Departments of Human and Molecular Genetics, Molecular and Cellular Biology, Molecular Physiology and Biophysics, and Pathology, Texas Children's Hospital, Howard Hughes Medical Institute, and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry, Departments of Human and Molecular Genetics, Molecular and Cellular Biology, Molecular Physiology and Biophysics, and Pathology, Texas Children's Hospital, Howard Hughes Medical Institute, and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Elledge","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry, Departments of Human and Molecular Genetics, Molecular and Cellular Biology, Molecular Physiology and Biophysics, and Pathology, Texas Children's Hospital, Howard Hughes Medical Institute, and Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,2,6]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80929-0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.425"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)82050-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80098-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80404-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5414.657"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.5.692"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80403-1"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5414.662"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)80021-4"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2001.6658"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101343200"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/35095068"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065203"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/35095076"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.21.7403-7415.2001"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.1.453"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr439"},{"key":"e_1_3_2_19_2","first-page":"7","volume":"29","year":"1997","unstructured":"Reed, S. I. (1997) Cancer Surv. 29, 7-23.9338094","journal-title":"Cancer Surv."},{"key":"e_1_3_2_20_2","first-page":"4535","volume":"62","year":"2002","unstructured":"Spruck, C. H., Strohmaier, H., Sangfelt, O., Muller, H. M., Hubalek, M., Muller-Holzner, E., Marth, C., Widschwendter, M. & Reed, S. I. (2002) Cancer Res. 62, 4535-4539.12183400","journal-title":"Cancer Res."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/45836"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.770"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8108"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80336-0"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80416-5"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80417-7"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/30756"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81193-9"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/19091"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290016"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(01)00676-2"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10208"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19981015)54:2<125::AID-JNR1>3.0.CO;2-G"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.23.3182"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1055"},{"key":"e_1_3_2_36_2","first-page":"737","volume":"115","year":"1992","unstructured":"Del Amo, F. F., Smith, D. E., Swiatek, P. J., Gendron-Maguire, M., Greenspan, R. J., McMahon, A. P. & Gridley, T. (1992) Development (Cambridge, U.K.) 115, 737-744.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(94)00257-F"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/383707a0"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(94)90081-7"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(96)00589-8"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(92)90076-S"},{"key":"e_1_3_2_42_2","first-page":"2251","volume":"122","year":"1996","unstructured":"Uyttendaele, H., Marazzi, G., Wu, G., Yan, Q., Sassoon, D. & Kitajewski, J. (1996) Development (Cambridge, U.K.) 122, 2251-2259.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_43_2","first-page":"199","volume":"113","year":"1991","unstructured":"Weinmaster, G., Roberts, V. J. & Lemke, G. (1991) Development (Cambridge, U.K.) 113, 199-205.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_44_2","first-page":"931","volume":"116","year":"1992","unstructured":"Weinmaster, G., Roberts, V. J. & Lemke, G. (1992) Development (Cambridge, U.K.) 116, 931-941.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(95)00451-3"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1993.1044"},{"key":"e_1_3_2_47_2","first-page":"1533","volume":"121","year":"1995","unstructured":"Conlon, R. A., Reaume, A. G. & Rossant, J. (1995) Development (Cambridge, U.K.) 121, 1533-1545.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_48_2","first-page":"3415","volume":"126","year":"1999","unstructured":"Hamada, Y., Kadokawa, Y., Okabe, M., Ikawa, M., Coleman, J. R. & Tsujimoto, Y. (1999) Development (Cambridge, U.K.) 126, 3415-3424.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/35016111"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00117-1"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.11.1343"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.6.707"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.4.2594-2599.1992"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90111-B"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.14.6414"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng797"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90385-R"},{"key":"e_1_3_2_58_2","first-page":"1705","volume":"129","year":"2002","unstructured":"Wei, L., Imanaka-Yoshida, K., Wang, L., Zhan, S., Schneider, M. D., DeMayo, F. J. & Schwartz, R. J. (2002) Development (Cambridge, U.K.) 129, 1705-1714.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_59_2","first-page":"839","volume":"126","year":"1999","unstructured":"Reecy, J. M., Li, X., Yamada, M., DeMayo, F. J., Newman, C. S., Harvey, R. P. & Schwartz, R. J. (1999) Development (Cambridge, U.K.) 126, 839-849.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.3.270"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9753"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5262.671"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.18.2375"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)80024-X"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/13886"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.13.2443"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10592"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0438008100"},{"key":"e_1_3_2_69_2","first-page":"3865","volume":"127","year":"2000","unstructured":"Rones, M. S., McLaughlin, K. A., Raffin, M. & Mercola, M. (2000) Development (Cambridge, U.K.) 127, 3865-3876.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008506200"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8384376"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.14.3.1669-1679.1994"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.21.2751"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00645-7"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0307875101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T09:47:54Z","timestamp":1649756874000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0307875101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,6]]},"references-count":74,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2004,3,9]]}},"alternative-id":["10.1073\/pnas.0307875101"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0307875101","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,2,6]]},"assertion":[{"value":"2004-02-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}