دورية أكاديمية
Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells
| العنوان: | Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells |
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| المؤلفون: | Ariadna Recasens, Sean J. Humphrey, Michael Ellis, Monira Hoque, Ramzi H. Abbassi, Brianna Chen, Mitchell Longworth, Elise J. Needham, David E. James, Terrance G. Johns, Bryan W. Day, Michael Kassiou, Pengyi Yang, Lenka Munoz |
| المصدر: | Cell Death Discovery, Vol 7, Iss 1, Pp 1-16 (2021) |
| بيانات النشر: | Nature Publishing Group, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens LCC:Cytology |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671 |
| الوصف: | Abstract Both tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins. DYRK1A inhibition leads to the accumulation of cyclin B and activation of CDK1. Importantly, we established that the phenotypic response of glioblastoma cells to DYRK1A inhibition depends on both retinoblastoma (RB) expression and the degree of residual DYRK1A activity. Moderate DYRK1A inhibition leads to moderate cyclin B accumulation, CDK1 activation and increased proliferation in RB-deficient cells. In RB-proficient cells, cyclin B/CDK1 activation in response to DYRK1A inhibition is neutralized by the RB pathway, resulting in an unchanged proliferation rate. In contrast, complete DYRK1A inhibition with high doses of inhibitors results in massive cyclin B accumulation, saturation of CDK1 activity and cell cycle arrest, regardless of RB status. These findings provide new insights into the complexity of context-dependent DYRK1A signalling in cancer cells. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2058-7716 |
| Relation: | https://doaj.org/toc/2058-7716 |
| DOI: | 10.1038/s41420-021-00456-6 |
| URL الوصول: | https://doaj.org/article/0a8dca1bb09e4683a7fb6162b88375d9 |
| رقم الأكسشن: | edsdoj.0a8dca1bb09e4683a7fb6162b88375d9 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20587716 |
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| DOI: | 10.1038/s41420-021-00456-6 |