GO:0010997 anaphase-promoting complex binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0010997 anaphase-promoting complex binding describes the molecular function of selectively binding to the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit ubiquitin ligase that triggers sister chromatid separation and mitotic exit.
• APC/C binding proteins include checkpoint components such as BubR1, which promotes Bub3-dependent APC/C inhibition during spindle assembly checkpoint signaling.
• The APC/C is regulated by structural interconversions and coactivators that determine substrate specificity and cell cycle timing.
• Metabolic signals such as lactate can remodel the APC/C and regulate cell cycle progression, linking APC/C binding to metabolic state.
• APC/C binding proteins also have non-mitotic functions, including roles in DNA methylation via degradation of DMS3 in Arabidopsis.
• D-box peptides can be developed to inhibit APC/C, providing tools to probe APC/C binding interfaces and substrate recognition.
Description
GO:0010997 anaphase-promoting complex binding is a molecular function term that describes the selective interaction of a protein with the anaphase-promoting complex/cyclosome (APC/C), a large multi-subunit ubiquitin ligase complex. The APC/C targets mitotic cyclins and anaphase inhibitory proteins for degradation, thereby triggering sister chromatid separation and exit from mitosis. Proteins that bind the APC/C can act as coactivators, inhibitors, or substrates, and their binding is often regulated by phosphorylation and cell cycle stage. Understanding this binding function is essential for dissecting how cells control chromosome segregation fidelity and how deregulation contributes to aneuploidy and cancer. Beyond mitosis, APC/C binding proteins participate in non-mitotic processes such as DNA methylation and metabolic regulation, expanding the biological scope of this GO term. Recent studies show that lactate can remodel the APC/C, directly linking metabolic signals to APC/C binding and cell cycle control. Additionally, engineered D-box peptides can inhibit APC/C, offering new ways to study APC/C binding interfaces and substrate recognition. This article integrates the QuickGO definition with verified PubMed literature to provide a research-grade overview of GO:0010997, its mechanisms, key genes, disease relevance, and experimental models.
anaphase-promoting complex binding At A Glance
| GO ID | GO:0010997 |
|---|---|
| GO term | anaphase-promoting complex binding |
| Ontology | molecular_function |
| Synonym | APC binding |
| Definition | Binding to an anaphase-promoting complex. A ubiquitin ligase complex that degrades mitotic cyclins and anaphase inhibitory protein, thereby triggering sister chromatid separation and exit from mitosis. |
| Major function | Selective interaction with the APC/C to regulate substrate recruitment, catalytic activation, or inhibition during cell cycle transitions. |
| Related processes | Mitotic exit, sister chromatid separation, spindle assembly checkpoint, DNA methylation, metabolic regulation. |
| Key cofactors | Cdc20, Cdh1, BubR1, Bub3, and D-box-containing substrates. |
What Is GO:0010997?
In our own words, GO:0010997 anaphase-promoting complex binding is the molecular function of physically and selectively interacting with the anaphase-promoting complex/cyclosome (APC/C). The APC/C is a ubiquitin ligase complex that degrades mitotic cyclins and anaphase inhibitory proteins, thereby triggering sister chromatid separation and exit from mitosis. This binding function is typically mediated by short linear motifs such as D-box or KEN-box degrons, or by coactivator subunits like Cdc20 and Cdh1, and it determines substrate recruitment, catalytic activation, or inhibition of the APC/C.
Why Is anaphase-promoting complex binding Important in Cell Biology?
GO:0010997 anaphase-promoting complex binding is critically important because it governs when and how the APC/C degrades its substrates, thereby controlling mitotic progression, chromosome segregation fidelity, and exit from mitosis. Deregulation of APC/C binding can lead to aneuploidy, genomic instability, and cancer, while non-mitotic APC/C functions influence DNA methylation and metabolic pathways. Moreover, metabolic signals such as lactate can remodel the APC/C, linking APC/C binding to cellular metabolism and providing new therapeutic angles. Understanding this binding function also enables the design of inhibitory peptides and small molecules that target APC/C-substrate interactions.
• Controls mitotic exit and sister chromatid separation by recruiting substrates to the APC/C.
• Regulates spindle assembly checkpoint signaling through BubR1-Bub3-dependent APC/C inhibition.
• Links metabolic state, such as lactate levels, to cell cycle progression via APC/C remodeling.
• Participates in non-mitotic functions including DNA methylation and transcriptional regulation.
• Deregulation contributes to aneuploidy and cancer, making APC/C binding a potential therapeutic target.
• Provides a basis for engineering D-box peptides that inhibit APC/C for research and drug development.
• Influences plant development and epigenetic regulation through APC/C-mediated degradation of DMS3.
• Offers a model system for studying protein-protein interaction motifs and ubiquitin ligase regulation.
• Enables functional studies using yeast two-hybrid, in vitro binding assays, and molecular simulation.
• Supports CRISPR-based functional genomics to dissect APC/C binding networks.
What Happens During anaphase-promoting complex binding?
Substrate Recognition and Docking
In simple terms: Proteins that bind the APC/C often carry short recognition tags that fit into pockets on the APC/C surface.
APC/C binding typically involves short linear motifs such as the D-box (destruction box) or KEN-box, which are recognized by coactivator subunits like Cdc20 or Cdh1. Structural studies show that the APC/C undergoes conformational changes that expose or hide these binding sites, thereby regulating substrate recruitment. D-box peptides can be engineered to competitively inhibit APC/C, confirming the importance of these motifs in binding.
Checkpoint Inhibition via BubR1-Bub3
In simple terms: During the spindle assembly checkpoint, a protein called BubR1 helps block the APC/C until chromosomes are properly attached.
BubR1 promotes Bub3-dependent APC/C inhibition during spindle assembly checkpoint signaling. This binding event prevents premature sister chromatid separation by blocking APC/C access to its substrates. The interaction between BubR1, Bub3, and the APC/C is a key regulatory node that ensures genomic stability.
Metabolic Remodeling of the APC/C
In simple terms: Cellular metabolites like lactate can change the APC/C structure and affect how it binds partners.
Lactate regulates the cell cycle by remodeling the anaphase promoting complex, directly linking metabolism to APC/C binding and function. This remodeling can alter substrate specificity and timing of mitotic exit. These findings expand the role of APC/C binding beyond classical cell cycle control.
Non-Mitotic APC/C Binding Functions
In simple terms: The APC/C also works outside of cell division, influencing processes like DNA methylation.
In Arabidopsis, the APC/C regulates RNA-directed DNA methylation activity by degrading DMS3, a non-mitotic function that depends on APC/C binding. Non-mitotic functions of the APC/C have been reviewed, highlighting roles in differentiation and development. These functions demonstrate that APC/C binding is not limited to mitosis.
Key Genes Involved in GO:0010997 anaphase-promoting complex binding
The following genes and proteins are central to anaphase-promoting complex binding, based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| BUBR1 | Promotes Bub3-dependent APC/C inhibition during spindle assembly checkpoint signaling | Checkpoint regulation and aneuploidy research |
| BUB3 | Binds BubR1 and contributes to APC/C inhibition | Spindle assembly checkpoint studies |
| CDC20 | APC/C coactivator that recognizes D-box substrates | Mitotic exit and substrate recruitment |
| CDH1 | APC/C coactivator that recognizes D-box and KEN-box substrates | Late mitosis and G1 regulation |
| APC10 | Core APC/C subunit involved in substrate binding | Interaction studies with glycolytic regulators |
| DMS3 | APC/C substrate in Arabidopsis, degraded to regulate RdDM | Plant epigenetic regulation |
| EhPpdk | Glycolytic regulator that interacts with APC10 | Metabolic-APC/C crosstalk |
| CCNB1 | Mitotic cyclin degraded by APC/C | Cell cycle control |
| PTTG1 | Anaphase inhibitor degraded by APC/C | Sister chromatid separation |
| D-box peptides | Engineered peptides that inhibit APC/C | Tool development for APC/C inhibition |
| Lactate | Metabolite that remodels APC/C | Metabolic regulation of mitosis |
| APC/C complex | Multi-subunit ubiquitin ligase | Structural and functional studies |
| Cdc20-APC/C | Active form targeting mitotic substrates | Mitotic progression |
| Cdh1-APC/C | Active form in late mitosis/G1 | G1 regulation |
| BubR1-Bub3 complex | Inhibitory complex binding APC/C | Checkpoint signaling |
| DMS3-APC/C | Non-mitotic substrate degradation | DNA methylation |
| EhApc10 | APC/C subunit in Entamoeba histolytica | Host-pathogen interaction |
How Is anaphase-promoting complex binding Regulated?
APC/C binding is regulated by multiple mechanisms, including phosphorylation of coactivators and substrates, conformational changes in the APC/C, and checkpoint proteins such as BubR1. Metabolic signals like lactate can remodel the APC/C, altering its binding properties. Additionally, D-box peptides can competitively inhibit APC/C binding, serving as experimental tools.
anaphase-promoting complex binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| BUBR1 | Aneuploidy, cancer | Knockout and point mutation cell lines |
| CDC20 | Cancer, mitotic defects | Overexpression and knockout models |
| CDH1 | Cancer, G1 arrest | Knock-in and knockout models |
| DMS3 | Epigenetic regulation in plants | Arabidopsis knockout |
| EhPpdk | Metabolic-APC/C crosstalk | Yeast two-hybrid and binding assays |
Cancer and Aneuploidy
Deregulation of APC/C binding can lead to aneuploidy and genomic instability, which are hallmarks of cancer. BubR1 mutations or altered expression impair checkpoint control, contributing to tumorigenesis. Targeting APC/C binding interfaces with D-box peptides may offer therapeutic strategies.
Metabolic Disorders
Lactate-mediated remodeling of the APC/C links APC/C binding to metabolic states, suggesting that metabolic disorders could impact cell cycle regulation. This crosstalk may be relevant in cancer metabolism and diabetes research.
Epigenetic and Developmental Disorders
Non-mitotic APC/C functions, such as degradation of DMS3 in Arabidopsis, affect DNA methylation and development. Disruption of these functions could contribute to epigenetic diseases.
From anaphase-promoting complex binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does BubR1 binding to APC/C require Bub3? | Knockout of BUB3 and BUBR1 |
| How does lactate remodel APC/C? | Point mutations in APC/C subunits |
| Can D-box peptides inhibit APC/C in cells? | Overexpression of D-box peptides |
| What are non-mitotic APC/C substrates? | Knock-in of tagged DMS3 |
| How does APC10 interact with glycolytic regulators? | Yeast two-hybrid and in vitro binding |
| What is the structural basis of APC/C binding? | Cryo-EM and molecular simulation |
How to Study the anaphase-promoting complex binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Yeast two-hybrid | Protein-protein interactions | Screening for APC/C binding partners |
| In vitro binding assay | Direct binding affinity | Validating APC/C-substrate interactions |
| Cryo-EM | Structural conformations | Visualizing APC/C binding interfaces |
| Molecular simulation | Binding dynamics | Modeling D-box peptide interactions |
| Flow cytometry | Cell cycle profiles | Assessing APC/C inhibition |
| Live-cell imaging | Mitotic progression | Tracking sister chromatid separation |
| Peptide inhibition assay | APC/C activity | Testing D-box peptides |
Yeast Two-Hybrid and In Vitro Binding Assays
Yeast two-hybrid screening and in vitro binding assays are used to detect interactions between APC/C subunits and partner proteins, such as EhPpdk and EhApc10. These methods help map binding interfaces and validate candidate interactions.
Structural Biology (Cryo-EM and Molecular Simulation)
Cryo-EM and molecular dynamics simulations reveal conformational changes and binding interfaces within the APC/C. These techniques are essential for understanding how D-box peptides and coactivators dock onto the APC/C.
Cell Cycle and Checkpoint Assays
Flow cytometry, live-cell imaging, and checkpoint assays measure how APC/C binding affects mitotic progression and spindle assembly checkpoint signaling. These assays are used to study BubR1-Bub3-dependent inhibition.
Peptide Inhibitor Development
D-box peptides are developed and tested for their ability to inhibit APC/C in vitro and in cells. This approach helps dissect the functional consequences of blocking APC/C binding.
How CRISPR Can Be Used to Study GO:0010997 anaphase-promoting complex binding
Knockout
CRISPR knockout of APC/C binding partners such as BUBR1 or BUB3 can reveal their roles in checkpoint signaling and mitotic progression. Knockout models are useful for studying loss-of-function phenotypes.
Point Mutation
Point mutations in D-box or KEN-box motifs can disrupt APC/C binding without affecting other functions, allowing precise structure-function studies. These models help identify critical residues for binding.
Knock-in
Knock-in of tagged APC/C subunits or substrates enables live-cell imaging and proteomic analysis of binding dynamics. Tagged knock-ins are valuable for tracking endogenous protein interactions.
Overexpression
Overexpression of APC/C coactivators or D-box peptides can modulate APC/C activity and binding, providing gain-of-function models. These models are used to test therapeutic potential.
How EDITGENE Supports anaphase-promoting complex binding Research
Researchers studying anaphase-promoting complex binding-related genes often need to determine whether a candidate gene is causally involved in APC/C regulation, substrate recruitment, or checkpoint control. EDITGENE provides CRISPR-based cell models and screening services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for anaphase-promoting complex binding research.
Frequently Asked Questions About anaphase-promoting complex binding
What is anaphase-promoting complex binding?
Anaphase-promoting complex binding (GO:0010997) is the molecular function of selectively interacting with the APC/C, a ubiquitin ligase that triggers sister chromatid separation and mitotic exit.
What genes are involved in anaphase-promoting complex binding?
Key genes include BUBR1, BUB3, CDC20, CDH1, APC10, and DMS3, among others.
How is APC/C binding regulated?
APC/C binding is regulated by phosphorylation, conformational changes, checkpoint proteins like BubR1, and metabolic signals such as lactate.
What diseases are linked to APC/C binding?
Deregulation of APC/C binding is linked to cancer, aneuploidy, and epigenetic disorders.
What methods study APC/C binding?
Yeast two-hybrid, in vitro binding assays, cryo-EM, molecular simulation, and cell cycle assays are commonly used.
Can CRISPR be used to study APC/C binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools for dissecting APC/C binding.
What are D-box peptides?
D-box peptides are engineered peptides that inhibit APC/C by competing with natural substrates for binding.
Does lactate affect APC/C binding?
Yes, lactate can remodel the APC/C and regulate cell cycle progression, linking metabolism to APC/C binding.
What are non-mitotic functions of APC/C binding?
Non-mitotic functions include regulation of DNA methylation via degradation of DMS3 in Arabidopsis.
How can EDITGENE help with APC/C binding research?
EDITGENE provides CRISPR cell models, library screening, and bioinformatics services to study APC/C binding mechanisms and disease relevance.
Conclusion
GO:0010997 anaphase-promoting complex binding is a central molecular function that controls mitotic progression, checkpoint signaling, and non-mitotic processes such as DNA methylation and metabolic regulation. Understanding its mechanisms, key genes, and disease links is essential for basic and translational research. EDITGENE offers comprehensive CRISPR solutions to accelerate discoveries in this field.
References
- 1. Liu W et al.. 2023. Lactate regulates cell cycle by remodelling the anaphase promoting complex.. Nature 616(7958):790-797 PMID: 36921622
- 2. Zhong S et al.. 2019. Anaphase-promoting complex/cyclosome regulates RdDM activity by degrading DMS3 in Arabidopsis.. Proc Natl Acad Sci U S A 116(9):3899-3908 PMID: 30760603
- 3. Eapen R et al.. 2025. Development of D-box peptides to inhibit the anaphase-promoting complex/cyclosome.. Elife 14 PMID: 40888475
- 4. Barford D. 2020. Structural interconversions of the anaphase-promoting complex/cyclosome (APC/C) regulate cell cycle transitions.. Curr Opin Struct Biol 61:86-97 PMID: 31864160
- 5. Dai X et al.. 2023. Lactate fuels mitosis.. Mol Cell 83(10):1549-1551 PMID: 37207623
- 6. Overlack K et al.. 2017. BubR1 Promotes Bub3-Dependent APC/C Inhibition during Spindle Assembly Checkpoint Signaling.. Curr Biol 27(19):2915-2927.e7 PMID: 28943088
- 7. Eguren M et al.. 2011. Non-mitotic functions of the Anaphase-Promoting Complex.. Semin Cell Dev Biol 22(6):572-8 PMID: 21439391
- 8. Pal S et al.. 2024. Unraveling the interaction between a glycolytic regulator protein EhPpdk and an anaphase promoting complex protein EhApc10: yeast two hybrid screening, in vitro binding assays and molecular simulation study.. Protein J 43(6):1104-1119 PMID: 39487362
