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Here, we characterized the role of KCTD15 in different physiological\/pathological states to gain insights into its diversified function(s). The silencing of KCTD15 in MLL-rearranged leukemia models induced attenuation of the NF-\u03baB pathway associated with a downregulation of pIKK-\u03b2 and pIKB-\u03b1. Conversely, the activation of peripheral blood T cells upon PMA\/ionomycin stimulation remarkably upregulated KCTD15 and, simultaneously, pIKK-\u03b2 and pIKB-\u03b1. Moreover, a significant upregulation of KCTD15 was also observed in CD34 hematopoietic stem\/progenitor cells where the NF-\u03baB pathway is physiologically activated. The association between KCTD15 upregulation and increased NF-\u03baB signaling was confirmed by luciferase assay as well as KCTD15 and IKK-\u03b2 proximity ligation and immunoprecipitation experiments. The observed upregulation of IKK-\u03b2 by KCTD15 provides a novel and intriguing interpretative key for understanding the protein function in a wide class of physiological\/pathological conditions ranging from neuronal development to cancer and obesity\/diabetes.<\/jats:p>","DOI":"10.1038\/s41598-021-97775-6","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T10:03:16Z","timestamp":1631613796000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["KCTD15 deregulation is associated with alterations of the NF-\u03baB signaling in both pathological and physiological model systems"],"prefix":"10.1038","volume":"11","author":[{"given":"Giovanni","family":"Smaldone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Coppola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Pane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Franzese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Beneduce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Parasole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Menna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Vitagliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Salvatore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peppino","family":"Mirabelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"97775_CR1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1053\/j.seminhematol.2018.08.002","volume":"56","author":"DA Arber","year":"2019","unstructured":"Arber, D. 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