{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T07:15:31Z","timestamp":1774768531564,"version":"3.50.1"},"reference-count":25,"publisher":"Proceedings of the National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,10,24]]},"abstract":"<jats:p>\n            Mutational inactivation of the adenomatous polyposis coli (APC)\n tumor suppressor initiates most hereditary and sporadic colon\n carcinomas. Although APC protein is located in both the cytoplasm and\n the nucleus, the protein domains required to maintain a predominantly\n cytoplasmic localization are unknown. Here, we demonstrate that nuclear\n export of APC is mediated by two intrinsic, leucine-rich, nuclear\n export signals (NESs) located near the amino terminus. Each NES was\n able to induce the nuclear export of a fused carrier protein. Both APC\n NESs were independently able to interact with the Crm1 nuclear export\n factor and substitute for the HIV-1 Rev NES to mediate nuclear mRNA\n export. Both APC NESs functioned within the context of APC sequence: an\n amino-terminal APC peptide containing both NESs interacted with Crm1\n and showed nuclear export in a heterokaryon nucleocytoplasmic shuttling\n assay. Also, mutation of both APC NESs resulted in the nuclear\n accumulation of the full-length, \u223c320-kDa APC protein, further\n establishing that the two intrinsic APC NESs are necessary for APC\n protein nuclear export. Moreover,\n            <jats:italic>endogenous<\/jats:italic>\n            APC accumulated in the nucleus of cells treated with the Crm1-specific\n nuclear export inhibitor leptomycin B. Together, these data indicate\n that APC is a nucleocytoplasmic shuttle protein whose predominantly\n cytoplasmic localization requires NES function and suggests that APC\n may be important for signaling between the nuclear and cytoplasmic\n compartments of epithelial cells.\n          <\/jats:p>","DOI":"10.1073\/pnas.220401797","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:45:09Z","timestamp":1027694709000},"page":"12085-12090","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":127,"title":["Adenomatous polyposis coli protein contains two nuclear export signals and shuttles between the nucleus and cytoplasm"],"prefix":"10.1073","volume":"97","author":[{"given":"Kristi L.","family":"Neufeld","sequence":"first","affiliation":[{"name":"Departments of Oncological Sciences and Biology,\r Huntsman Cancer Institute, University of Utah, Salt Lake City, UT\r 84112; and Howard Hughes Medical Institute and Department\r of Genetics, Duke University Medical Center, Durham, NC 27710"}]},{"given":"David A.","family":"Nix","sequence":"additional","affiliation":[{"name":"Departments of Oncological Sciences and Biology,\r Huntsman Cancer Institute, University of Utah, Salt Lake City, UT\r 84112; and Howard Hughes Medical Institute and Department\r of Genetics, Duke University Medical Center, Durham, NC 27710"}]},{"given":"Hal","family":"Bogerd","sequence":"additional","affiliation":[{"name":"Departments of Oncological Sciences and Biology,\r Huntsman Cancer Institute, University of Utah, Salt Lake City, UT\r 84112; and Howard Hughes Medical Institute and Department\r of Genetics, Duke University Medical Center, Durham, NC 27710"}]},{"given":"Yibin","family":"Kang","sequence":"additional","affiliation":[{"name":"Departments of Oncological Sciences and Biology,\r Huntsman Cancer Institute, University of Utah, Salt Lake City, UT\r 84112; and Howard Hughes Medical Institute and Department\r of Genetics, Duke University Medical Center, Durham, NC 27710"}]},{"given":"Mary C.","family":"Beckerle","sequence":"additional","affiliation":[{"name":"Departments of Oncological Sciences and Biology,\r Huntsman Cancer Institute, University of Utah, Salt Lake City, UT\r 84112; and Howard Hughes Medical Institute and Department\r of Genetics, Duke University Medical Center, Durham, NC 27710"}]},{"given":"Bryan R.","family":"Cullen","sequence":"additional","affiliation":[{"name":"Departments of Oncological Sciences and Biology,\r Huntsman Cancer Institute, University of Utah, Salt Lake City, UT\r 84112; and Howard Hughes Medical Institute and Department\r of Genetics, Duke University Medical Center, Durham, NC 27710"}]},{"given":"Raymond L.","family":"White","sequence":"additional","affiliation":[{"name":"Departments of Oncological Sciences and Biology,\r Huntsman Cancer Institute, University of Utah, Salt Lake City, UT\r 84112; and Howard Hughes Medical Institute and Department\r of Genetics, Duke University Medical Center, Durham, NC 27710"}]}],"member":"341","published-online":{"date-parts":[[2000,10,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/359235a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.3046"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5264.1023"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1790"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3290209"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(08)60381-6"},{"key":"e_1_3_3_7_2","first-page":"591","volume":"10","author":"Miyoshi Y","year":"1998","unstructured":"Y Miyoshi, K Iwao, G Nawa, H Yoshikawa, T Ochi, Y Nakamura Oncol Res 10, 591\u2013594 (1998).","journal-title":"Oncol Res"},{"key":"e_1_3_3_8_2","first-page":"1130","volume":"58","author":"Sparks A B","year":"1998","unstructured":"A B Sparks, P J Morin, B Vogelstein, K W Kinzler Cancer Res 58, 1130\u20131134 (1998).","journal-title":"Cancer Res"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.7.3034"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.10.3151"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9588"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/11064"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.134.1.165"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.5.1139"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2144\/97224bm11"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.11.8627-8635.1998"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.8.4248-4254.1991"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.12b.2496"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.9.4421"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.19.7787"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90119-1"},{"key":"e_1_3_3_22_2","first-page":"3676","volume":"54","author":"Munemitsu S","year":"1994","unstructured":"S Munemitsu, B Souza, O Muller, I Albert, B Rubinfeld, P Polakis Cancer Res 54, 3676\u20133681 (1994).","journal-title":"Cancer Res"},{"key":"e_1_3_3_23_2","first-page":"3672","volume":"54","author":"Smith K","year":"1994","unstructured":"K Smith, D Levy, P Maupin, T Pollard, B Vogelstein, K Kinzler Cancer Res 54, 3672\u20133675 (1994).","journal-title":"Cancer Res"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/36894"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(99)00016-7"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.220401797","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T12:12:08Z","timestamp":1649851928000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.220401797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,10,17]]},"references-count":25,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2000,10,24]]}},"alternative-id":["10.1073\/pnas.220401797"],"URL":"https:\/\/doi.org\/10.1073\/pnas.220401797","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,10,17]]},"assertion":[{"value":"2000-08-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-10-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}