ArticleNature communications2022
Inhibition of the CDK2 and Cyclin A complex leads to autophagic degradation of CDK2 in cancer cells.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 112 citations in OpenAlex.
- Targeting CDK2 ameliorates allergic asthma through suppression of epithelial chemokine production and T cell inflammatory responses.Science China. Life sciences · 2026Article
- Integrated multi-omics analysis reveals the molecular landscape and therapeutic strategies in Chinese cervical cancer patients.PLoS biology · 2026Article
- Adaptive mechanisms and emerging cancer therapeutics for CDK2 inhibitors.Nature chemical biology · 2026Review
- Machine Learning and Virtual Screening Methods to Discover Potential Cyclin-Dependent Kinase 2 (CDK2) Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Diversity and Multi-Target Potential of Pyrazole, Imidazole or Triazole Derivatives in Modern Anticancer Therapy.International journal of molecular sciences · 2026Review
- Molecular Mechanisms Underlying the Anti-Cancer Effects of Tangeretin, a Phytochemical from Citrus Extracts.Biomolecules & therapeutics · 2026Review
- Homoharringtonine inhibits growth and migration in non-small cell lung cancer via PDIA4-mediated modulation of autophagy and EMT.Archives of pharmacal research · 2026Article
- miR-215-5p Suppresses Proliferation/Cell-Cycle Progression and Promotes Apoptosis via Targeting CTCF in Goat Mammary Epithelial Cells.Animals : an open access journal from MDPI · 2026Article
- Advances in molecular glue degraders for targeted protein degradation: Focus on NEK7, WEE1, CDK2, GSPT1 and VAV1.Asian journal of pharmaceutical sciences · 2026Review
- ALYREF-mediated mInternational journal of biological sciences · 2026Article
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- TRIM21 and OTUD6A orchestrate AKT K27-linked atypical ubiquitination to modulate cancer chemoresistance.Nature structural & molecular biology · 2026Article
- The Role of CDKs in the Regulation of the Monocyte/Macrophage Immune Response.Current medicinal chemistry · 2026Review
- Design, synthesis, and evaluation of novel pinane-based thiazolidione derivatives with anti-glioblastoma activity.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Molecular Docking and Target-Specific Binding Profiles of Benzosuberane-Based Compounds.ChemMedChem · 2025Review
- Exploiting targeted degradation of cyclins and cyclin-dependent kinases for cancer therapeutics: a review.Journal of Zhejiang University. Science. B · 2025Review
- Uncovering Anti-Melanoma Mechanisms ofInternational journal of molecular sciences · 2025Article
- MicroRNA-18b regulates cell cycle progression in papillary thyroid carcinoma by targetingAnnals of surgical treatment and research · 2025Article
- Ubiquitin-conjugating enzyme UBE2N modulates proteostasis in immunoproteasome-positive acute myeloid leukemia.The Journal of clinical investigation · 2025Article
- TRIM21-mediated METTL3 degradation promotes PDAC ferroptosis and enhances the efficacy of Anti-PD-1 immunotherapy.Cell death & disease · 2025Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
Cyclin-dependent kinase 2 (CDK2) complex is significantly over-activated in many cancers. While it makes CDK2 an attractive target for cancer therapy, most inhibitors against CDK2 are ATP competitors that are either nonspecific or highly toxic, and typically fail clinical trials. One alternative approach is to develop non-ATP competitive inhibitors; they disrupt interactions between CDK2 and either its partners or substrates, resulting in specific inhibition of CDK2 activities. In this report, we identify two potential druggable pockets located in the protein-protein interaction interface (PPI) between CDK2 and Cyclin A. To target the potential druggable pockets, we perform a LIVS in silico screening of a library containing 1925 FDA approved drugs. Using this approach, homoharringtonine (HHT) shows high affinity to the PPI and strongly disrupts the interaction between CDK2 and cyclins. Further, we demonstrate that HHT induces autophagic degradation of the CDK2 protein via tripartite motif 21 (Trim21) in cancer cells, which is confirmed in a leukemia mouse model and in human primary leukemia cells. These results thus identify an autophagic degradation mechanism of CDK2 protein and provide a potential avenue towards treating CDK2-dependent cancers.
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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.