ArticleProceedings of the National Academy of Sciences of the United States of America2019
Inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 2 perturbs 26S proteasome-addicted neoplastic progression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Current Research in Polypharmacology for Cancer Treatment Using Dual-Target Histone Deacetylase Inhibitors.International journal of molecular sciences · 2026Review
- DYRK2 drives renal fibrosis through CDK1-dependent G2/M phase dysregulation in tubular epithelial cells.Cellular & molecular biology letters · 2026Article
- The dual fate of DYRK2 in cancer: balancing the light and dark side of tumorigenesis.Cancer metastasis reviews · 2026Review
- The effect of deuterated PLK1 inhibitor on its safety and efficacyFrontiers in oncology · 2025Article
- The diverse functions of DYRK2 in response to cellular stress.Histology and histopathology · 2024Review
- Integration of scHi-C and scRNA-seq data defines distinct 3D-regulated and biological-context dependent cell subpopulations.Nature communications · 2024Article
- One-pot synthesis of tetrahydropyrimidinecarboxamides enablingRSC advances · 2024Article
- CircCOX6A1 suppresses osteogenic differentiation and aggravates osteoporosis via miR-512-3p/DYRK2 axis.Molecular biology reports · 2024Article
- Discovery of the First Potent DYRK2 Proteolysis Targeting Chimera Degraders.ACS medicinal chemistry letters · 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
- Chemoproteomics, A Broad Avenue to Target Deconvolution.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Functional Roles of DYRK2 as a Tumor Regulator.Current issues in molecular biology · 2023Review
- FBXW7 tumor suppressor regulation by dualspecificity tyrosine-regulated kinase 2.Cell death & disease · 2023Article
- Integrative transcriptome analysis of SARS-CoV-2 human-infected cells combined with deep learning algorithms identifies two potential cellular targets for the treatment of coronavirus disease.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Article
- Dual inhibition of HSF1 and DYRK2 impedes cancer progression.Bioscience reports · 2023Article
- The prognostic value of 19S ATPase proteasome subunits in acute myeloid leukemia and other forms of cancer.Frontiers in medicine · 2023Article
- Gut microbiota deficiency ameliorates multiple myeloma and myeloma-related bone disease by Th17 cells in mice models.Journal of Cancer · 2023Article
- Synthesis ofAnnals of medicine · 2022Article
- One-pot two-step catalytic synthesis of 6-amino-2-pyridone-3,5-dicarbonitriles enabling anti-cancer bioactivity.RSC advances · 2022Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 3 countries.
Funding
Abstract
Dependence on the 26S proteasome is an Achilles' heel for triple-negative breast cancer (TNBC) and multiple myeloma (MM). The therapeutic proteasome inhibitor, bortezomib, successfully targets MM but often leads to drug-resistant disease relapse and fails in breast cancer. Here we show that a 26S proteasome-regulating kinase, DYRK2, is a therapeutic target for both MM and TNBC. Genome editing or small-molecule mediated inhibition of DYRK2 significantly reduces 26S proteasome activity, bypasses bortezomib resistance, and dramatically delays in vivo tumor growth in MM and TNBC thereby promoting survival. We further characterized the ability of LDN192960, a potent and selective DYRK2-inhibitor, to alleviate tumor burden in vivo. The drug docks into the active site of DYRK2 and partially inhibits all 3 core peptidase activities of the proteasome. Our results suggest that targeting 26S proteasome regulators will pave the way for therapeutic strategies in MM and TNBC.
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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.