{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:58:19Z","timestamp":1791341899823,"version":"4.3.1"},"reference-count":88,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T00:00:00Z","timestamp":1705017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["PAI77200098"],"award-info":[{"award-number":["PAI77200098"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>NSD3 (nuclear receptor-binding SET domain protein 3) is a member of the NSD histone methyltransferase family of proteins. In recent years, it has been identified as a potential oncogene in certain types of cancer. The NSD3 gene encodes three isoforms, the long version (NSD3L), a short version (NSD3S) and the WHISTLE isoforms. Importantly, the NSD3S isoform corresponds to the N-terminal region of the full-length protein, lacking the methyltransferase domain. The chromosomal location of NSD3 is frequently amplified across cancer types, such as breast, lung, and colon, among others. Recently, this amplification has been correlated to a chromothripsis event, that could explain the different NSD3 alterations found in cancer. The fusion proteins containing NSD3 have also been reported in leukemia (NSD3-NUP98), and in NUT (nuclear protein of the testis) midline carcinoma (NSD3-NUT). Its role as an oncogene has been described by modulating different cancer pathways through its methyltransferase activity, or the short isoform of the protein, through protein interactions. Specifically, in this review we will focus on the functions that have been characterized as methyltransferase dependent, and those that have been correlated with the expression of the NSD3S isoform. There is evidence that both the NSD3L and NSD3S isoforms are relevant for cancer progression, establishing NSD3 as a therapeutic target. However, further functional studies are needed to differentiate NSD3 oncogenic activity as dependent or independent of the catalytic domain of the protein, as well as the contribution of each isoform and its clinical significance in cancer progression.<\/jats:p>","DOI":"10.3390\/ijms25020944","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T07:47:16Z","timestamp":1705045636000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["NSD3 in Cancer: Unraveling Methyltransferase-Dependent and Isoform-Specific Functions"],"prefix":"10.3390","volume":"25","author":[{"given":"Yanara","family":"Nu\u00f1ez","sequence":"first","affiliation":[{"name":"Biomedical Science Research Laboratory, Department of Basic Sciences, Faculty of Medicine, Universidad Cat\u00f3lica de la Sant\u00edsima Concepci\u00f3n, Concepci\u00f3n 4090541, Chile"},{"name":"Biochemistry, Faculty of Pharmacy, Universidad de Concepci\u00f3n, Concepci\u00f3n 4070383, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Vera","sequence":"additional","affiliation":[{"name":"Biomedical Science Research Laboratory, Department of Basic Sciences, Faculty of Medicine, Universidad Cat\u00f3lica de la Sant\u00edsima Concepci\u00f3n, Concepci\u00f3n 4090541, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Baeza","sequence":"additional","affiliation":[{"name":"Biomedical Science Research Laboratory, Department of Basic Sciences, Faculty of Medicine, Universidad Cat\u00f3lica de la Sant\u00edsima Concepci\u00f3n, Concepci\u00f3n 4090541, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Gonzalez-Pecchi","sequence":"additional","affiliation":[{"name":"Biomedical Science Research Laboratory, Department of Basic Sciences, Faculty of Medicine, Universidad Cat\u00f3lica de la Sant\u00edsima Concepci\u00f3n, Concepci\u00f3n 4090541, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0092-8674(00)81958-3","article-title":"Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome","volume":"98","author":"Kornberg","year":"1999","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.cell.2007.05.009","article-title":"High-Resolution Profiling of Histone Methylations in the Human Genome","volume":"129","author":"Barski","year":"2007","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S0959-437X(02)00287-3","article-title":"Histone Methylation in Transcriptional Control","volume":"12","author":"Kouzarides","year":"2002","journal-title":"Curr. 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