{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:03:10Z","timestamp":1765976590127,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG2014-15197"],"award-info":[{"award-number":["IG2014-15197"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nucleostemin (NS; a product of the GNL3 gene) is a nucleolar\u2013nucleoplasm shuttling GTPase whose levels are high in stem cells and rapidly decrease upon differentiation. NS levels are also high in several solid and hematological neoplasms, including acute myeloid leukaemia (AML). While a role in telomere maintenance, response to stress stimuli and favoring DNA repair has been proposed in solid cancers, little or no information is available as to the role of nucleostemin in AML. Here, we investigate this issue via a proteomics approach. We use as a model system the OCI-AML 3 cell line harboring a heterozygous mutation at the NPM1 gene, which is the most frequent driver mutation in AML (approximately 30% of total AML cases). We show that NS is highly expressed in this cell line, and, contrary to what has previously been shown in other cancers, that its presence is dispensable for cell growth and viability. However, proteomics analysis of the OCI-AML 3 cell line before and after nucleostemin (NS) silencing showed several effects on different biological functions, as highlighted by ingenuity pathway analysis (IPA). In particular, we report an effect of down-regulating DNA repair through homologous recombination, and we confirmed a higher DNA damage rate in OCI-AML 3 cells when NS is depleted, which considerably increases upon stress induced by the topoisomerase II inhibitor etoposide. The data used are available via ProteomeXchange with the identifier PXD034012.<\/jats:p>","DOI":"10.3390\/ijms23147655","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T21:57:53Z","timestamp":1657576673000},"page":"7655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Proteomic Investigation of the Role of Nucleostemin in Nucleophosmin-Mutated OCI-AML 3 Cell Line"],"prefix":"10.3390","volume":"23","author":[{"given":"Ilaria","family":"Cela","sequence":"first","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6457-7795","authenticated-orcid":false,"given":"Maria Concetta","family":"Cufaro","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-3705","authenticated-orcid":false,"given":"Maurine","family":"Fucito","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-3484","authenticated-orcid":false,"given":"Damiana","family":"Pieragostino","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Lanuti","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Medicine and Aging Science, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2555-3571","authenticated-orcid":false,"given":"Michele","family":"Sallese","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1653-2194","authenticated-orcid":false,"given":"Piero","family":"Del Boccio","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5921-7365","authenticated-orcid":false,"given":"Adele","family":"Di Matteo","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council of Italy, P.le Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-8085","authenticated-orcid":false,"given":"Nerino","family":"Allocati","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"De Laurenzi","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Federici","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1101\/gad.55671","article-title":"A Nucleolar Mechanism Controlling Cell Proliferation in Stem Cells and Cancer Cells","volume":"16","author":"Tsai","year":"2002","journal-title":"Genes 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