ArticleCell death and differentiation2022
A novel CDC25A/DYRK2 regulatory switch modulates cell cycle and survival.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 65 citations in OpenAlex.
- Identification of Ferroptosis-related Genes Associated with the Prognosis of Hepatocellular Carcinoma.Cell biochemistry and biophysics · 2026Article
- Long-Term PET-Nanoplastic Exposure Alters DNA Damage Response Capacity in BEAS-2B Human Bronchial Epithelial Cells.International journal of molecular sciences · 2026Article
- Identification and experimental validation of biomarkers associated with integrated stress response in sepsis.Biochemistry and biophysics reports · 2026Article
- DYRK2 drives renal fibrosis through CDK1-dependent G2/M phase dysregulation in tubular epithelial cells.Cellular & molecular biology letters · 2026Article
- CMGC Kinases in Viral Infection and Human Disease.Pathogens (Basel, Switzerland) · 2026Review
- 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
- Identification of a Novel miR-122-5p/CDC25A Axis and Potential Therapeutic Targets for Chronic Myeloid Leukemia.International journal of molecular sciences · 2025Article
- ARRB2 promotes cervical cancer progression via stabilizing CDC25A mRNA through m6A-IGF2BP1-dependent manner.NPJ precision oncology · 2025Article
- Melatonin ameliorates zearalenone-induced ovarian damage in mice through antioxidative effects.Frontiers in veterinary science · 2025Article
- Investigating the causal role of cellular senescence-related genes in preeclampsia: a multi-omics Mendelian randomization study with differential expression analysis.Frontiers in endocrinology · 2025Article
- Cynaroside Induces G1 Cell Cycle Arrest by Downregulating Cell Division Cycle 25A in Colorectal Cancer.Molecules (Basel, Switzerland) · 2024Article
- Nasal polyp antibody-secreting cells display proliferation signature in aspirin-exacerbated respiratory disease.The Journal of allergy and clinical immunology · 2024Article
- A novel avian intestinal epithelial cell line: its characterization and exploration as an in vitro infection culture model for Eimeria species.Parasites & vectors · 2024Article
- Localization, traffic and function of Rab34 in adipocyte lipid and endocrine functions.Journal of biomedical science · 2024Article
- Dissecting Ubiquitylation and DNA Damage Response Pathways in the Yeast Saccharomyces cerevisiae Using a Proteome-Wide Approach.Molecular & cellular proteomics : MCP · 2024Article
- Functional Roles of DYRK2 as a Tumor Regulator.Current issues in molecular biology · 2023Review
- Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.FEBS letters · 2023Review
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- New insights into the roles for DYRK family in mammalian development and congenital diseases.Genes & diseases · 2023Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
The cell division cycle 25A (CDC25A) phosphatase is a key regulator of cell cycle progression that acts on the phosphorylation status of Cyclin-Cyclin-dependent kinase complexes, with an emergent role in the DNA damage response and cell survival control. The regulation of CDC25A activity and its protein level is essential to control the cell cycle and maintain genomic integrity. Here we describe a novel ubiquitin/proteasome-mediated pathway negatively regulating CDC25A stability, dependent on its phosphorylation by the serine/threonine kinase DYRK2. DYRK2 phosphorylates CDC25A on at least 7 residues, resulting in its degradation independent of the known CDC25A E3 ubiquitin ligases. CDC25A in turn is able to control the phosphorylation of DYRK2 at several residues outside from its activation loop, thus affecting DYRK2 localization and activity. An inverse correlation between DYRK2 and CDC25A protein amounts was observed during cell cycle progression and in response to DNA damage, with CDC25A accumulation responding to the manipulation of DYRK2 levels or activity in either physiological scenario. Functional data show that the pro-survival activity of CDC25A and the pro-apoptotic activity of DYRK2 could be partly explained by the mutual regulation between both proteins. Moreover, DYRK2 modulation of CDC25A expression and/or activity contributes to the DYRK2 role in cell cycle regulation. Altogether, we provide evidence suggesting that DYRK2 and CDC25A mutually control their activity and stability by a feedback regulatory loop, with a relevant effect on the genotoxic stress pathway, apoptosis, and cell cycle regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.