ArticleThe EMBO journal1999
Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers.
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Who cites it
169 citing papers in PubMed, 422 citations in OpenAlex.
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- CDT1 acts with the replisome to remodel replication forks.Science advances · 2026Article
- H3K4me3 and H3K27ac Promote ccRCC Proliferation Through the CDC6-EXOSC5 Axis.International journal of molecular sciences · 2026Article
- Cyclin-E/A/CDK1/2 Kinetic Landscapes Drive Cell Cycle Phase-Specific Progression and Guide Cyclin-E Degradation Strategy.Journal of chemical information and modeling · 2026Article
- Etiology of polyploid giant cancer cells: a new frontier in cancer biology.Cancer cell international · 2026Review
- Integrated Bioinformatics Analysis and Experimental Validation of the Role of Cellular Senescence in Osteoporosis.Calcified tissue international · 2025Article
- Temporal control of human DNA replication licensing by CDK4/6-RB signalling and chemical genetics.Nature communications · 2025Article
- Yeast culture in weaned lamb feed: a proteomic journey into enhanced rumen health and growth.Journal of animal science and biotechnology · 2025Article
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- Carotenoids Modulate FoxO-Induced Cell Cycle Awrrest in Human Cancer Cell Lines: A Scoping Review.Food science & nutrition · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- SKP2 inhibition activates tumor cell-intrinsic immunity by inducing DNA replication stress and genomic instability.British journal of cancer · 2025Article
- NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2.Journal of cell science · 2024Article
- Circular RNAs in Cell Cycle Regulation of Cancers.International journal of molecular sciences · 2024Review
- CDK4/6 inhibitor-induced bone marrow micronuclei might be caused by cell cycle arrest during erythropoiesis.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2024Article
- The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.International journal of molecular sciences · 2023Review
- CDC6 as a Key Inhibitory Regulator of CDK1 Activation Dynamics and the Timing of Mitotic Entry and Progression.Biology · 2023Review
- Cyclins and cyclin-dependent kinases: from biology to tumorigenesis and therapeutic opportunities.Journal of cancer research and clinical oncology · 2023Review
- Critical DNA damaging pathways in tumorigenesis.Seminars in cancer biology · 2022Review
- Quantitative profiling of adaptation to cyclin E overproduction.Life science alliance · 2022Article
109 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent kinases (CDKs) are essential for regulating key transitions in the cell cycle, including initiation of DNA replication, mitosis and prevention of re-replication. Here we demonstrate that mammalian CDC6, an essential regulator of initiation of DNA replication, is phosphorylated by CDKs. CDC6 interacts specifically with the active Cyclin A/CDK2 complex in vitro and in vivo, but not with Cyclin E or Cyclin B kinase complexes. The cyclin binding domain of CDC6 was mapped to an N-terminal Cy-motif that is similar to the cyclin binding regions in p21(WAF1/SDI1) and E2F-1. The in vivo phosphorylation of CDC6 was dependent on three N-terminal CDK consensus sites, and the phosphorylation of these sites was shown to regulate the subcellular localization of CDC6. Consistent with this notion, we found that the subcellular localization of CDC6 is cell cycle regulated. In G1, CDC6 is nuclear and it relocalizes to the cytoplasm when Cyclin A/CDK2 is activated. In agreement with CDC6 phosphorylation being specifically mediated by Cyclin A/CDK2, we show that ectopic expression of Cyclin A, but not of Cyclin E, leads to rapid relocalization of CDC6 from the nucleus to the cytoplasm. Based on our data we suggest that the phosphorylation of CDC6 by Cyclin A/CDK2 is a negative regulatory event that could be implicated in preventing re-replication during S phase and G2.
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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.