{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:22:40Z","timestamp":1790882560678,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T00:00:00Z","timestamp":1644624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"POR FES\/FESR","award":["POR FES\/FESR 2014-20-ATS ALCMEONE cup J18C17000610006"],"award-info":[{"award-number":["POR FES\/FESR 2014-20-ATS ALCMEONE cup J18C17000610006"]}]},{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["MIUR-PRIN 2017MHJJ55_002"],"award-info":[{"award-number":["MIUR-PRIN 2017MHJJ55_002"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The IBTK gene encodes the IBtk\u03b1 protein that is a substrate receptor of E3 ubiquitin ligase, Cullin 3. We have previously reported the pro-tumorigenic activity of Ibtk in MYC-dependent B-lymphomagenesis observed in E\u03bc-myc transgenic mice. Here, we provide mechanistic evidence of the functional interplay between IBtk\u03b1 and MYC. We show that IBtk\u03b1, albeit indirectly, activates the \u03b2-catenin-dependent transcription of the MYC gene. Of course, IBtk\u03b1 associates with GSK3\u03b2 and promotes its ubiquitylation, which is associated with proteasomal degradation. This event increases the protein level of \u03b2-catenin, a substrate of GSK3\u03b2, and results in the transcriptional activation of the MYC and CCND1 target genes of \u03b2-catenin, which are involved in the control of cell division and apoptosis. In particular, we found that in Burkitt\u2019s lymphoma cells, IBtk\u03b1 silencing triggered the downregulation of both MYC mRNA and protein expression, as well as a strong decrease of cell survival, mainly through the induction of apoptotic events, as assessed by using flow cytometry-based cell cycle and apoptosis analysis. Collectively, our results shed further light on the complex puzzle of IBtk\u03b1 interactome and highlight IBtk\u03b1 as a potential novel therapeutic target to be employed in the strategy for personalized therapy of B cell lymphoma.<\/jats:p>","DOI":"10.3390\/ijms23042044","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T21:08:43Z","timestamp":1644786523000},"page":"2044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["IBtk\u03b1 Activates the \u03b2-Catenin-Dependent Transcription of MYC through Ubiquitylation and Proteasomal Degradation of GSK3\u03b2 in Cancerous B Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-2679","authenticated-orcid":false,"given":"Eleonora","family":"Vecchio","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro \u2018Magna Graecia\u2019, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3784-7446","authenticated-orcid":false,"given":"Nancy","family":"Nistic\u00f2","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro \u2018Magna Graecia\u2019, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetanina","family":"Golino","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro \u2018Magna Graecia\u2019, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3565-7817","authenticated-orcid":false,"given":"Enrico","family":"Iaccino","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro \u2018Magna Graecia\u2019, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1221-9320","authenticated-orcid":false,"given":"Domenico","family":"Maisano","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro \u2018Magna Graecia\u2019, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2187-9176","authenticated-orcid":false,"given":"Selena","family":"Mimmi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro \u2018Magna Graecia\u2019, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Aloisio","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro \u2018Magna Graecia\u2019, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Renna","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Avagliano","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Arcucci","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5414-6190","authenticated-orcid":false,"given":"Giuseppe","family":"Fiume","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro \u2018Magna Graecia\u2019, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana","family":"Quinto","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro \u2018Magna Graecia\u2019, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1093\/nar\/gkn413","article-title":"Physical and functional characterization of the genetic locus of IBtk, an inhibitor of Bruton\u2019s tyrosine kinase: Evidence for three protein isoforms of IBtk","volume":"36","author":"Spatuzza","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.compbiolchem.2009.08.001","article-title":"Computational analysis and in vivo validation of a microRNA 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