ArticleProceedings of the National Academy of Sciences of the United States of America2024
The Mitotic Checkpoint Complex controls the association of Cdc20 regulatory protein with the ubiquitin ligase APC/C in mitosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- A CDC20 allelic series reveals stage-specific control of metaphase-to-anaphase transitions during mitosis and meiosis in rice.Science China. Life sciences · 2026Article
- Comparative Functional Effects of Abemaciclib and Arcyriaflavin A inInternational journal of molecular sciences · 2026Article
- PCIPG2.0: multi-omics fusion and structure-aware graph autoencoding for protein complex identification.Bioinformatics (Oxford, England) · 2026Article
- BubR1 TPR domain supports the mitotic checkpoint by promoting MCC formation and MCC-APC/C interaction.Communications biology · 2026Article
- CDC20 promotes prostate cancer progression via modulating c-MYC and PI3K-AKT signaling.iScience · 2026Article
- Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies.Molecular biomedicine · 2026Review
- TRIM37 recognizes a bipartite degron to ubiquitinate centrosome substrates.bioRxiv : the preprint server for biology · 2025Article
- Dynamics of spindle assembly and position checkpoints: Integrating molecular mechanisms with computational models.Computational and structural biotechnology journal · 2025Review
- Network-based insights into miR-30a-5p-mediated regulation and EGCG targeting in triple-negative breast cancer.Frontiers in bioinformatics · 2025Article
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Abstract
The ubiquitin ligase Anaphase-Promoting Complex/Cyclosome (APC/C) and its regulatory protein Cdc20 play important roles in the control of different stages of mitosis. APC/C associated with Cdc20 is active and promotes metaphase-anaphase transition by targeting for degradation inhibitors of anaphase initiation. Earlier in mitosis, premature action of APC/C is prevented by the mitotic checkpoint (or spindle assembly checkpoint) system, which ensures that anaphase is not initiated until all chromosomes are properly attached to the mitotic spindle. The active mitotic checkpoint system promotes the assembly of a Mitotic Checkpoint Complex (MCC), which binds to APC/C and inhibits its activity. The interaction of MCC with APC/C is strongly enhanced by Cdc20 bound to APC/C. While the association of Cdc20 with APC/C was known to be essential for both these stages of mitosis, it was not known how Cdc20 remains bound in spite of ongoing processes, phosphorylation and ubiquitylation, that stimulate its release from APC/C. We find that MCC strongly inhibits the release of Cdc20 from APC/C by the action of mitotic protein kinase Cdk1-cyclin B. This is not due to protection from phosphorylation of specific sites in Cdc20 that affect its interaction with APC/C. Rather, MCC stabilizes the binding to APC/C of partially phosphorylated forms of Cdc20. MCC also inhibits the autoubiquitylation of APC/C-bound Cdc20 and its ubiquitylation-promoted release from APC/C. We propose that these actions of MCC to maintain Cdc20 bound to APC/C in mitosis are essential for the control of mitosis during active mitotic checkpoint and in subsequent anaphase initiation.
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