دورية أكاديمية
IBtkα Activates the β-Catenin-Dependent Transcription of MYC through Ubiquitylation and Proteasomal Degradation of GSK3β in Cancerous B Cells
| العنوان: | IBtkα Activates the β-Catenin-Dependent Transcription of MYC through Ubiquitylation and Proteasomal Degradation of GSK3β in Cancerous B Cells |
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| المؤلفون: | Eleonora Vecchio, Nancy Nisticò, Gaetanina Golino, Enrico Iaccino, Domenico Maisano, Selena Mimmi, Annamaria Aloisio, Maurizio Renna, Angelica Avagliano, Alessandro Arcucci, Giuseppe Fiume, Ileana Quinto |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 4, p 2044 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | MYC, β-catenin, GSK3β, Burkitt’s lymphoma, IBtkα, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | The IBTK gene encodes the IBtkα 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 Eμ-myc transgenic mice. Here, we provide mechanistic evidence of the functional interplay between IBtkα and MYC. We show that IBtkα, albeit indirectly, activates the β-catenin-dependent transcription of the MYC gene. Of course, IBtkα associates with GSK3β and promotes its ubiquitylation, which is associated with proteasomal degradation. This event increases the protein level of β-catenin, a substrate of GSK3β, and results in the transcriptional activation of the MYC and CCND1 target genes of β-catenin, which are involved in the control of cell division and apoptosis. In particular, we found that in Burkitt’s lymphoma cells, IBtkα 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 IBtkα interactome and highlight IBtkα as a potential novel therapeutic target to be employed in the strategy for personalized therapy of B cell lymphoma. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 23042044 1422-0067 1661-6596 |
| العلاقة: | https://www.mdpi.com/1422-0067/23/4/2044Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms23042044 |
| الوصول الحر: | https://doaj.org/article/cac33e3108204da28ca6bad0c7650706Test |
| رقم الانضمام: | edsdoj.33e3108204da28ca6bad0c7650706 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23042044 14220067 16616596 |
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| DOI: | 10.3390/ijms23042044 |