{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:02:33Z","timestamp":1789372953415,"version":"build-2803163510"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,3,14]]},"abstract":"<jats:p>\n                    Loss of the cyclin-dependent kinase inhibitor p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    leads to an overall increase in animal growth, pituitary tumors, and hyperplasia of hematopoietic organs, yet it is unknown whether all cells function autonomously in response to p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    activity or whether certain cells take cues from their neighbors. In addition, there is currently no genetic evidence that tumor suppression by p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    is cell-autonomous because biallelic gene inactivation is absent from tumors arising in p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    hemizygous mice. We have addressed these questions with tissue-specific targeted mouse mutants and radiation chimeras. Our results indicate that the suppression of pars intermedia pituitary tumors by p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    is cell-autonomous and does not contribute to overgrowth or infertility phenotypes. In contrast, suppression of spleen growth and hematopoietic progenitor expansion is a consequence of p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    function external to the hematopoietic compartment. Likewise, p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    suppresses thymocyte hyperplasia through a cell-nonautonomous mechanism. The interaction of p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    loss with epithelial cell-specific cyclin-dependent kinase 4 overexpression identifies the thymic epithelium as a relevant site of p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    activity for the regulation of thymus growth.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0509514103","type":"journal-article","created":{"date-parts":[[2006,3,3]],"date-time":"2006-03-03T20:25:43Z","timestamp":1141417543000},"page":"4122-4127","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":36,"title":["Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27\n                    <sup>Kip1<\/sup>"],"prefix":"10.1073","volume":"103","author":[{"given":"Wei-Ming","family":"Chien","sequence":"first","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Rabin","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everardo","family":"Macias","sequence":"additional","affiliation":[{"name":"Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula L.","family":"Miliani de Marval","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra","family":"Garrison","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Orthel","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Rodriguez-Puebla","sequence":"additional","affiliation":[{"name":"Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Fero","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,3,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81239-8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81238-6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81237-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.18.2899"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.2.306"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/24179"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/81335"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1214"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6270"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.13.4889"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03179835"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.7634"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.4.1269-1277.2003"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.2.714"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61703-8"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64616-0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206163"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6382"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203490"},{"key":"e_1_3_3_20_2","first-page":"787","volume":"9","author":"Tong W.","year":"1998","unstructured":"W. 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