ArticleCellular and molecular life sciences : CMLS2020
Phosphorylation-dependent regulation of the NOTCH1 intracellular domain by dual-specificity tyrosine-regulated kinase 2.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- The dual fate of DYRK2 in cancer: balancing the light and dark side of tumorigenesis.Cancer metastasis reviews · 2026Review
- A novel feedback loop between DYRK2 and USP28 regulates cancer homeostasis and DNA damage signaling.Cell death and differentiation · 2026Article
- Optimized Monothiol Thioredoxin Derivative (ORP100S) Protects In Vitro and In Vivo from Radiation and Chemotoxicity Without Promoting Tumor Proliferation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.Life science alliance · 2025Article
- DUSP6 regulates Notch1 signalling in colorectal cancer.Nature communications · 2024Article
- The diverse functions of DYRK2 in response to cellular stress.Histology and histopathology · 2024Review
- Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management.International journal of molecular sciences · 2024Review
- Functional Roles of DYRK2 as a Tumor Regulator.Current issues in molecular biology · 2023Review
- The mitochondrial ribosomal protein mRpL4 regulates Notch signaling.EMBO reports · 2023Article
- FBXW7 tumor suppressor regulation by dualspecificity tyrosine-regulated kinase 2.Cell death & disease · 2023Article
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- A novel CDC25A/DYRK2 regulatory switch modulates cell cycle and survival.Cell death and differentiation · 2022Article
- The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues.Cancer reports (Hoboken, N.J.) · 2021Review
- Betulinic Acid Hydroxamate is Neuroprotective and Induces Protein Phosphatase 2A-Dependent HIF-1α Stabilization and Post-transcriptional Dephosphorylation of Prolyl Hydrolase 2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.Nature communications · 2021Article
- Notch-ing up knowledge on molecular mechanisms of skin fibrosis: focus on the multifaceted Notch signalling pathway.Journal of biomedical science · 2021Review
- GSK3β Interacts With CRMP2 and Notch1 and Controls T-Cell Motility.Frontiers in immunology · 2021Article
- Updating dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2): molecular basis, functions and role in diseases.Cellular and molecular life sciences : CMLS · 2020Review
- The DYRK Family of Kinases in Cancer: Molecular Functions and Therapeutic Opportunities.Cancers · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
NOTCH proteins constitute a receptor family with a widely conserved role in cell cycle, growing and development regulation. NOTCH1, the best characterised member of this family, regulates the expression of key genes in cell growth and angiogenesis, playing an essential role in cancer development. These observations provide a relevant rationale to propose the inhibition of the intracellular domain of NOTCH1 (Notch1-IC) as a strategy for treating various types of cancer. Notch1-IC stability is mainly controlled by post-translational modifications. FBXW7 ubiquitin E3 ligase-mediated degradation is considered one of the most relevant, being the previous phosphorylation at Thr-2512 residue required. In the present study, we describe for the first time a new regulation mechanism of the NOTCH1 signalling pathway mediated by DYRK2. We demonstrate that DYRK2 phosphorylates Notch1-IC in response to chemotherapeutic agents and facilitates its proteasomal degradation by FBXW7 ubiquitin ligase through a Thr-2512 phosphorylation-dependent mechanism. We show that DYRK2 regulation by chemotherapeutic agents has a relevant effect on the viability, motility and invasion capacity of cancer cells expressing NOTCH1. In summary, we reveal a novel mechanism of regulation for NOTCH1 which might help us to better understand its role in cancer biology.
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