ArticleNature communications2015
Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human cancer cells.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- Temporal control of human DNA replication licensing by CDK4/6-RB signalling and chemical genetics.Nature communications · 2025Article
- Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions.Discover oncology · 2025Article
- Notch controls APC/CScience advances · 2025Article
- Inhibition of GPX4 enhances CDK4/6 inhibitor and endocrine therapy activity in breast cancer.Nature communications · 2024Article
- APC/C prevents a noncanonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Reciprocal antagonism of PIN1-APC/CNature communications · 2024Article
- Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell.bioRxiv : the preprint server for biology · 2024Article
- Advances in the mechanism of CDK4/6 inhibitor resistance in HR+/HER2- breast cancer.Therapeutic advances in medical oncology · 2024Review
- Strategy of combining CDK4/6 inhibitors with other therapies and mechanisms of resistance.International journal of clinical and experimental pathology · 2024Review
- APC/C prevents non-canonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.bioRxiv : the preprint server for biology · 2023Article
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- Abemaciclib Is Effective in Palbociclib-Resistant Hormone Receptor-Positive Metastatic Breast Cancers.Cancer research · 2023Article
- Progression after First-Line Cyclin-Dependent Kinase 4/6 Inhibitor Treatment: Analysis of Molecular Mechanisms and Clinical Data.International journal of molecular sciences · 2023Review
- The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities.Nature structural & molecular biology · 2023Article
- Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Breast Cancer Patients: Who Would Benefit from Neoadjuvant Chemotherapies?Current oncology (Toronto, Ont.) · 2022Review
- MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon.Journal of Crohn's & colitis · 2022Article
- Insufficiency of FZR1 disturbs HSC quiescence by inhibiting ubiquitin-dependent degradation of RUNX1 in aplastic anemia.Leukemia · 2022Article
- CDK4 and CDK6 kinases: From basic science to cancer therapy.Science (New York, N.Y.) · 2022Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Cyclin-dependent kinases 4 and 6 (CDK4/6) in complex with D-type cyclins promote cell cycle entry. Most human cancers contain overactive CDK4/6-cyclin D, and CDK4/6-specific inhibitors are promising anti-cancer therapeutics. Here, we investigate the critical functions of CDK4/6-cyclin D kinases, starting from an unbiased screen in the nematode Caenorhabditis elegans. We found that simultaneous mutation of lin-35, a retinoblastoma (Rb)-related gene, and fzr-1, an orthologue to the APC/C co-activator Cdh1, completely eliminates the essential requirement of CDK4/6-cyclin D (CDK-4/CYD-1) in C. elegans. CDK-4/CYD-1 phosphorylates specific residues in the LIN-35 Rb spacer domain and FZR-1 amino terminus, resembling inactivating phosphorylations of the human proteins. In human breast cancer cells, simultaneous knockdown of Rb and FZR1 synergistically bypasses cell division arrest induced by the CDK4/6-specific inhibitor PD-0332991. Our data identify FZR1 as a candidate CDK4/6-cyclin D substrate and point to an APC/C(FZR1) activity as an important determinant in response to CDK4/6-inhibitors.
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