Emerging roles of DYRK2 in cancer
| العنوان: | Emerging roles of DYRK2 in cancer |
|---|---|
| المؤلفون: | Vasudha Tandon, Sourav Banerjee, Laureano de la Vega |
| المصدر: | The Journal of Biological Chemistry |
| بيانات النشر: | American Society for Biochemistry and Molecular Biology, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, STAT3, signal transducer and activator of transcription 3, NSCLC, non–small-cell lung cancer, Review, NAPA, N-terminal autophosphorylation accessory, Biochemistry, stress, HIPK2, homeodomain-interacting protein kinase, TANK-binding kinase 1, Heat Shock Transcription Factors, Neoplasms, Phosphorylation, HSF1, Triple-negative breast cancer, E3 ligase, NOTCH1, neurogenic locus notch homolog protein 1, biology, Kinase, MM, multiple myeloma, protein kinase, Protein-Tyrosine Kinases, Prognosis, Ubiquitin ligase, PEST, Pro-Glu-Ser-Thr, EMT, epithelial–mesenchymal transition, Ser62, serine62, Thr58, Threonine58, Proteasome Endopeptidase Complex, kinase inhibitor, Protein Serine-Threonine Kinases, Ser727, serine727, TNBC, triple-negative breast cancer, 03 medical and health sciences, CML, chronic myeloid leukemia, medicine, Humans, IFN, interferon, Molecular Biology, proteostasis, 030102 biochemistry & molecular biology, CMGC, Cyclin-dependent kinases, Mitogen-activated protein kinases, Glycogen synthase kinases, and CDC-like kinases, Cancer, Cell Biology, HSF1, heat-shock factor 1, medicine.disease, GEMMs, genetically engineered mouse models, 030104 developmental biology, Proteostasis, proteasome, Proteasome, DYRK, Dual-specificity tYrosine phosphorylation–Regulated Kinase, TBK1, TANK-binding kinase 1, biology.protein, Cancer research, TCGA, The Cancer Genome Atlas, Tumor Suppressor Protein p53 |
| الوصف: | Over the last decade, the CMGC kinase DYRK2 has been reported as a tumor suppressor across various cancers triggering major antitumor and proapoptotic signals in breast, colon, liver, ovary, brain, and lung cancers, with lower DYRK2 expression correlated with poorer prognosis in patients. Contrary to this, various medicinal chemistry studies reported robust antiproliferative properties of DYRK2 inhibitors, whereas unbiased ‘omics' and genome-wide association study-based studies identified DYRK2 as a highly overexpressed kinase in various patient tumor samples. A major paradigm shift occurred in the last 4 years when DYRK2 was found to regulate proteostasis in cancer via a two-pronged mechanism. DYRK2 phosphorylated and activated the 26S proteasome to enhance degradation of misfolded/tumor-suppressor proteins while also promoting the nuclear stability and transcriptional activity of its substrate, heat-shock factor 1 triggering protein folding. Together, DYRK2 regulates proteostasis and promotes protumorigenic survival for specific cancers. Indeed, potent and selective small-molecule inhibitors of DYRK2 exhibit in vitro and in vivo anti-tumor activity in triple-negative breast cancer and myeloma models. However, with conflicting and contradictory reports across different cancers, the overarching role of DYRK2 remains enigmatic. Specific cancer (sub)types coupled to spatiotemporal interactions with substrates could decide the procancer or anticancer role of DYRK2. The current review aims to provide a balanced and critical appreciation of the literature to date, highlighting top substrates such as p53, c-Myc, c-Jun, heat-shock factor 1, proteasome, or NOTCH1, to discuss DYRK2 inhibitors available to the scientific community and to shed light on this duality of protumorigenic and antitumorigenic roles of DYRK2. |
| اللغة: | English |
| تدمد: | 1083-351X 0021-9258 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::061eea48deade93ca0fc9f31e939d4a2 http://europepmc.org/articles/PMC7948649 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....061eea48deade93ca0fc9f31e939d4a2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1083351X 00219258 |
|---|