{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:16:26Z","timestamp":1784556986734,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/deed.en_GB"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:p>\n                    Inactivating germline mutations of the\n                    <jats:italic>CDKN1B<\/jats:italic>\n                    gene encoding the nuclear cyclin-dependent kinase inhibitor P27\n                    <jats:sup>kip1<\/jats:sup>\n                    protein have been reported in patients with multiple endocrine neoplasia type 4 (MEN4), a MEN1-like phenotype without\n                    <jats:italic>MEN1<\/jats:italic>\n                    mutations. The aim of this study was to characterize\n                    <jats:italic>in vitro<\/jats:italic>\n                    the germline\n                    <jats:italic>CDKN1B<\/jats:italic>\n                    mutation c.374_375delCT (S125X) we detected in a patient with MEN4. The proband was affected by primary hyperparathyroidism due to multiglandular parathyroid involvement and gastro\u2013entero\u2013pancreatic tumors. We carried out subcellular localization experiments by transfection with plasmid vectors expressing the WT or mutant\n                    <jats:italic>CDKN1B<\/jats:italic>\n                    cDNA into the eukaryotic human cervix adenocarcinoma (HeLa) and GH3 cell lines. Results from western blotting studies indicated that fusion proteins were expressed at equal levels. The mutated protein was shorter compared with the WT protein and lacked the highly conserved C-terminal domain, which includes the bipartite nuclear localization signal at amino acids 152\/153 and 166\/168. In HeLa and GH3 cells, WT P27 localized in the nucleus, whereas the P27_S125X protein was retained in the cytoplasm, predicting the loss of tumor-suppressive function. The proband's tumoral parathyroid tissue did not show allelic loss, because both WT and mutant alleles were determined to be present by sequencing the somatic DNA. Immunohistochemistry revealed a complete loss of nuclear expression of P27 in a parathyroid adenoma, which had been removed by the second surgery in the patient. In conclusion, our results confirm the pathogenic role of the c.374_375delCT\n                    <jats:italic>CDKN1B<\/jats:italic>\n                    germline mutation in a patient with MEN4.\n                  <\/jats:p>","DOI":"10.1530\/ec-14-0116","type":"journal-article","created":{"date-parts":[[2014,11,21]],"date-time":"2014-11-21T21:09:55Z","timestamp":1416604195000},"page":"1-8","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":31,"title":["Functional characterization of a CDKN1B mutation in a Sardinian kindred with multiple endocrine neoplasia type 4"],"prefix":"10.1530","volume":"4","author":[{"given":"Elena","family":"Pardi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Mariotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia S","family":"Pellegata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katiuscia","family":"Benfini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Borsari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Saponaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liborio","family":"Torregrossa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Cappai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Satta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mastinu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Marcocci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Cetani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/4\/1\/1.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/4\/1\/1.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:41:52Z","timestamp":1784554912000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/4\/1\/1-8\/35111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/ec-14-0116","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3]]}}}