GO:0005680 anaphase-promoting complex: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0005680 defines the anaphase-promoting complex (APC/C), a multi-subunit E3 ubiquitin ligase that triggers sister chromatid separation and mitotic exit by degrading mitotic cyclins and anaphase inhibitory proteins.
• APC/C substrate recognition depends on degradation signals, most commonly the D-box motif originally found in cyclin B.
• APC/C activity is tightly regulated by coactivators CDC20 and CDH1, phosphorylation, and reversible inhibition by the spindle assembly checkpoint.
• Beyond mitosis, APC/C controls neuronal differentiation, metabolic reprogramming, and cellular ageing.
• Deregulated APC/C is implicated in cancer, neurodegenerative disorders, and age-related pathologies, making it a therapeutic target.
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable precise dissection of APC/C subunit and substrate functions.
Description
The anaphase-promoting complex, also known as the cyclosome (APC/C), is a large multi-subunit E3 ubiquitin ligase that serves as a master regulator of cell division. It was originally identified as the activity responsible for the ubiquitin-dependent degradation of mitotic cyclins, a process required for exit from mitosis. Subsequent work established that APC/C also targets anaphase inhibitory proteins such as securin, thereby triggering sister chromatid separation. Because APC/C coordinates both the onset of anaphase and the termination of mitosis, its activity must be precisely controlled in space and time. Over the past two decades, APC/C has emerged as a versatile regulator beyond the cell cycle, influencing neuronal development, metabolism, and ageing. Its dysfunction is linked to cancer, neurodegeneration, and age-related diseases, making it a compelling target for basic and translational research. Understanding APC/C composition, assembly, and regulation is therefore essential for researchers in cell cycle biology, neurobiology, and oncology. This article provides a research-grade overview of GO:0005680, covering its definition, structure, molecular mechanism, key genes, disease relevance, and experimental methods, including CRISPR-based models for functional interrogation.
anaphase-promoting complex At A Glance
| GO ID | GO:0005680 |
|---|---|
| GO term | anaphase-promoting complex |
| Ontology | cellular_component |
| Synonym | anaphase promoting complex; APC; cyclosome |
| Major function | Ubiquitin ligase complex that degrades mitotic cyclins and anaphase inhibitory proteins, triggering sister chromatid separation and exit from mitosis |
| Substrate recognition | Degradation signals, most commonly the D-box motif originally discovered in cyclin B |
| Cofactors | CDC20 and CDH1 (FZR1) activate APC/C for distinct substrate sets |
| Regulation | Phosphorylation, spindle assembly checkpoint, and reversible inhibitor binding |
| Disease links | Cancer, neurodegeneration, ageing-related pathologies |
What Is GO:0005680?
GO:0005680 describes the anaphase-promoting complex (APC/C), a ubiquitin ligase complex that degrades mitotic cyclins and anaphase inhibitory proteins, thereby triggering sister chromatid separation and exit from mitosis. Substrate recognition by APC/C occurs through degradation signals, the most common of which is the D-box motif originally discovered in cyclin B. The complex is also known as the cyclosome and functions as a multi-subunit E3 ligase that polyubiquitinates target proteins for proteasomal degradation.
Why Is anaphase-promoting complex Important in Cell Biology?
APC/C is essential for faithful chromosome segregation and mitotic exit, and its deregulation leads to aneuploidy, genomic instability, and disease. Beyond mitosis, APC/C controls neuronal differentiation, metabolic reprogramming, and cellular ageing, making it a central node in multiple physiological and pathological contexts. Because APC/C substrates include oncoproteins and tumor suppressors, the complex is a promising target for anticancer strategies, including combination with drugs that induce multipolar mitotic spindles.
• APC/C triggers sister chromatid separation by degrading securin, allowing separase activation.
• It promotes mitotic exit by degrading mitotic cyclins.
• APC/C is essential for neuronal differentiation and brain development.
• It regulates cellular ageing and senescence pathways.
• APC/C controls metabolic reprogramming, including lactate-mediated cell cycle regulation.
• Its deregulation contributes to cancer and neurodegeneration.
• APC/C is a target for anticancer strategies that exploit mitotic spindle defects.
• It coordinates with phosphatases to ensure mitotic fidelity.
• APC/C substrate recognition via D-box and KEN-box motifs enables selective degradation.
• CRISPR models enable precise functional dissection of APC/C subunits and substrates.
Structure and Composition of anaphase-promoting complex
Overall architecture and subunit organization
In simple terms: APC/C is a large molecular machine made of many protein subunits that work together to tag other proteins for destruction.
The APC/C is a multi-subunit E3 ubiquitin ligase complex composed of approximately 14 core subunits in humans, including scaffolding proteins, cullin-like subunits, and substrate-recognition modules. Its architecture is conserved from yeast to plants and mammals, with plant APC/C also containing specific subunits. The complex forms a platform that positions E2 ubiquitin-conjugating enzymes and substrates for efficient ubiquitin transfer.
Catalytic core and cullin-RING module
In simple terms: A central catalytic engine within APC/C adds ubiquitin tags to target proteins.
The catalytic core of APC/C includes the cullin-like subunit APC2 and the RING-H2 domain protein APC11, which together recruit E2 enzymes and catalyze ubiquitin chain formation. This module is structurally related to other cullin-RING ligases but is uniquely regulated by APC/C-specific subunits. The D-box receptor subunit APC10 contributes to substrate recognition and processive ubiquitination.
Coactivator binding and substrate recruitment
In simple terms: Helper proteins called coactivators plug into APC/C and decide which targets get destroyed.
APC/C activity requires binding of a coactivator, either CDC20 or CDH1 (FZR1), which provides a substrate-recognition surface for D-box and KEN-box motifs. CDC20 activates APC/C during early mitosis, while CDH1 functions later in mitosis and in G1. The coactivator also interacts with the spindle assembly checkpoint protein complex to delay APC/C activation until chromosomes are properly attached.
Assembly and dynamic remodeling
In simple terms: APC/C is built from preformed subcomplexes and can change its shape to perform different tasks.
APC/C assembles from preformed subcomplexes, including the APC1-APC4-APC5 module and the APC2-APC11 catalytic module, which come together with other subunits to form the holoenzyme. Structural studies have revealed conformational changes upon coactivator binding that reposition the catalytic site for optimal ubiquitin transfer. In plants, APC/C assembly and regulation involve additional plant-specific subunits and post-translational modifications.
Regulatory subunits and inhibitors
In simple terms: Special proteins can bind APC/C and put the brakes on its activity.
The spindle assembly checkpoint proteins, including MAD2, BUBR1, and BUB3, inhibit APC/C by sequestering CDC20 until all chromosomes are correctly attached to the spindle. Additional regulators such as EMI1 and the pseudosubstrate inhibitor APC15 modulate APC/C activity and ensure timely substrate degradation. Phosphorylation of APC/C subunits by mitotic kinases such as CDK1 and PLK1 also regulates its function.
Key Genes Involved in GO:0005680 anaphase-promoting complex
The following genes encode core subunits, coactivators, and regulators of the anaphase-promoting complex (GO:0005680) that are commonly studied in cell cycle, neurobiology, and cancer research.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ANAPC1 | Core scaffold subunit (APC1) | Essential for complex assembly; mutations linked to mitotic defects |
| ANAPC2 | Catalytic cullin-like subunit (APC2) | Forms catalytic core with APC11; target for functional studies |
| ANAPC3 | TPR subunit (APC3/Cdc27) | Scaffold for coactivator binding; involved in substrate recruitment |
| ANAPC4 | Core subunit (APC4) | Part of APC1-APC4-APC5 module; required for holoenzyme assembly |
| ANAPC5 | TPR subunit (APC5) | Interacts with coactivators; regulates APC/C activity |
| ANAPC7 | TPR subunit (APC7) | Contributes to substrate recognition; studied in cancer models |
| ANAPC10 | D-box receptor (APC10/Doc1) | Directly binds D-box motifs; critical for substrate targeting |
| ANAPC11 | RING-H2 catalytic subunit (APC11) | Recruits E2 enzymes; essential for ubiquitin transfer |
| CDC20 | Coactivator (CDC20) | Activates APC/C in mitosis; target of spindle assembly checkpoint |
| CDH1 (FZR1) | Coactivator (CDH1) | Activates APC/C in late mitosis/G1; regulates neuronal differentiation |
| MAD2L1 | Spindle assembly checkpoint protein (MAD2) | Inhibits APC/C by sequestering CDC20 |
| BUB1B | Spindle assembly checkpoint kinase (BUBR1) | Regulates APC/C inhibition and chromosome segregation |
| CCNB1 | Mitotic cyclin B1 | Key APC/C substrate; degradation triggers mitotic exit |
| PTTG1 | Securin | APC/C substrate; degradation activates separase for sister chromatid separation |
| FBXO5 | EMI1 | APC/C inhibitor; regulates mitotic entry and exit |
| PLK1 | Polo-like kinase 1 | Phosphorylates APC/C subunits; regulates activation |
| CDK1 | Cyclin-dependent kinase 1 | Phosphorylates APC/C; coordinates mitotic events |
How Is anaphase-promoting complex Regulated?
APC/C is regulated at multiple levels. The spindle assembly checkpoint (SAC) inhibits APC/C by sequestering CDC20 until all chromosomes are properly attached to the mitotic spindle. Phosphorylation by CDK1 and PLK1 modulates APC/C subunit interactions and coactivator binding. Reversible inhibitor EMI1 (FBXO5) binds APC/C during S and G2 phases to prevent premature activation. Phosphatases such as PP2A counteract mitotic phosphorylation to fine-tune APC/C activity. In addition, metabolic signals such as lactate can remodel APC/C to influence cell cycle progression.
anaphase-promoting complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CDC20 | Cancer (multiple types); poor prognosis | Knockout or overexpression in cancer cell lines; xenograft models |
| CDH1 (FZR1) | Neurodegeneration; neuronal survival | Conditional knockout in mouse neurons; iPSC-derived neurons |
| ANAPC1 | Mitotic defects; cancer predisposition | CRISPR knockout in cell lines; organoids |
| PTTG1 | Cancer; chromosomal instability | Point mutation of D-box; knock-in reporter |
| MAD2L1 | Aneuploidy; cancer | Knockout in cell lines; SAC assays |
APC/C in cancer
Deregulation of APC/C subunits or coactivators leads to aneuploidy and genomic instability, hallmarks of cancer. Overexpression of CDC20 is observed in many cancers and correlates with poor prognosis. Targeting APC/C-CDC20 activity enhances the effectiveness of anticancer drugs that induce multipolar mitotic spindles, suggesting a therapeutic strategy.
APC/C in neurodegeneration
APC/C plays critical roles in neuronal differentiation, axon growth, and synapse formation. Dysregulation of APC/C has been implicated in neurodegenerative conditions, including Alzheimer's disease and Parkinson's disease, where aberrant cell cycle re-entry contributes to neuronal death. CDH1 (FZR1) is particularly important for neuronal survival and function.
APC/C in ageing
APC/C is a cellular ageing regulator, influencing senescence and organismal lifespan. Its activity declines with age, contributing to the accumulation of damaged proteins and genomic instability. Modulating APC/C activity may therefore have therapeutic potential for age-related diseases.
APC/C in metabolic regulation
Lactate regulates the cell cycle by remodeling the anaphase promoting complex, linking metabolism to cell division. This metabolic control of APC/C has implications for cancer metabolism and tissue regeneration.
From anaphase-promoting complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| What is the role of APC/C subunit X in mitosis? | CRISPR knockout cell lines (e.g., HeLa, HEK293T) |
| How does a specific D-box mutation affect substrate degradation? | Point-mutation knock-in of substrate D-box |
| What is the dynamics of APC/C activation in live cells? | Tagged knock-in of APC/C subunits with fluorescent proteins |
| Does overexpression of CDC20 drive tumorigenesis? | Overexpression cell models and xenografts |
| How does APC/C regulate neuronal differentiation? | Conditional knockout in mouse brain or iPSC-derived neurons |
| What is the impact of APC/C on ageing? | Knockout or overexpression in model organisms (e.g., mice, Drosophila) |
How to Study the anaphase-promoting complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Mitotic progression and chromosome segregation | Assessing APC/C knockout phenotypes |
| In vitro ubiquitination assay | Ubiquitin chain formation on substrates | Measuring APC/C catalytic activity |
| Cycloheximide chase | Substrate half-life | Validating D-box-dependent degradation |
| Mass spectrometry proteomics | APC/C interactome and substrate identification | Mapping APC/C network |
| RNA-seq | Transcriptional changes upon APC/C perturbation | Identifying downstream pathways |
| CRISPR library screening | Genetic dependencies and synthetic lethality | Discovering APC/C-related vulnerabilities |
| Flow cytometry | Cell cycle profile and DNA content | Detecting mitotic defects |
| Immunofluorescence | Subcellular localization of APC/C subunits | Visualizing APC/C at kinetochores and spindle |
Cell cycle and mitotic assays
Flow cytometry, live-cell imaging of fluorescently tagged histones or tubulin, and time-lapse microscopy are used to monitor mitotic progression and chromosome segregation upon APC/C perturbation. These methods reveal delays in metaphase-to-anaphase transition and defects in mitotic exit.
Ubiquitination and degradation assays
In vitro ubiquitination assays with recombinant APC/C and E2 enzymes, combined with western blotting for substrate stability, measure APC/C catalytic activity. Cycloheximide chase assays assess substrate half-life in cells.
Proteomics and interactomics
Mass spectrometry-based proteomics identifies APC/C subunits, interactors, and ubiquitinated substrates. Proximity labeling (BioID) and immunoprecipitation coupled to mass spectrometry map the APC/C interactome.
Transcriptomics and functional genomics
RNA-seq and CRISPR library screening reveal transcriptional changes and genetic dependencies associated with APC/C loss or overexpression. These approaches identify synthetic lethal interactions and pathways that buffer APC/C dysfunction.
How CRISPR Can Be Used to Study GO:0005680 anaphase-promoting complex
Knockout
CRISPR knockout of APC/C subunits (e.g., ANAPC1, ANAPC2, CDC20) in cell lines abrogates complex function, causing mitotic arrest or slippage. These models are used to study subunit-specific roles and to identify compensatory pathways.
Point Mutation
Point mutations in APC/C subunit catalytic residues or in substrate D-box motifs can be introduced via CRISPR to dissect mechanism without complete loss of protein. Such models reveal the importance of specific residues for ubiquitin transfer or substrate recognition.
Knock-in
Knock-in of fluorescent or affinity tags into endogenous APC/C subunit loci enables live-cell imaging and proteomic analysis of the complex at physiological expression levels. Tagged knock-in models are valuable for tracking APC/C dynamics during the cell cycle.
Overexpression
CRISPR-mediated overexpression (e.g., via safe-harbor integration) of CDC20 or CDH1 allows gain-of-function studies to assess oncogenic potential and substrate degradation kinetics. Overexpression models complement knockout approaches to define dosage-sensitive effects.
How EDITGENE Supports anaphase-promoting complex Research
Researchers studying anaphase-promoting complex-related genes often need to determine whether a candidate gene is causally involved in mitotic regulation, substrate degradation, or disease phenotypes. EDITGENE provides a comprehensive suite of CRISPR-based services to generate precisely engineered cell models, enabling rigorous functional validation of APC/C components and their substrates.
Contact EDITGENE today to design your custom CRISPR model for anaphase-promoting complex research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CUL7 Knockout HEK293 Cell Line | EDJ-KQ1883 | Human | 9820 | Details Get a Quote |
| FZR1 Knockout HEK293 Cell Line | EDJ-KQ3137 | Human | 51343 | Details Get a Quote |
| UBE2S Knockout HEK293 Cell Line | EDJ-KQ3959 | Human | 27338 | Details Get a Quote |
| UBE2C Knockout HEK293 Cell Line | EDJ-KQ7264 | Human | 11065 | Details Get a Quote |
| ANAPC16 Knockout HEK293 Cell Line | EDJ-KQ7640 | Human | 119504 | Details Get a Quote |
| ANAPC13 Knockout HEK293 Cell Line | EDJ-KQ8262 | Human | 25847 | Details Get a Quote |
| ANAPC7 Knockout HEK293 Cell Line | EDJ-KQ11092 | Human | 51434 | Details Get a Quote |
| CDC20B Knockout HEK293 Cell Line | EDJ-KQ12835 | Human | 166979 | Details Get a Quote |
| FZR1 Knockout A-549 Cell Line | EDJ-KQ23131 | Human | 51343 | Details Get a Quote |
| CUL7 Knockout A-549 Cell Line | EDJ-KQ23137 | Human | 9820 | Details Get a Quote |
| CUL7 Knockout HCT 116 Cell Line | EDJ-KQ23138 | Human | 9820 | Details Get a Quote |
| CUL7 Knockout HeLa Cell Line | EDJ-KQ23139 | Human | 9820 | Details Get a Quote |
| ANAPC16 Knockout A-549 Cell Line | EDJ-KQ33000 | Human | 119504 | Details Get a Quote |
| ANAPC16 Knockout HCT 116 Cell Line | EDJ-KQ33001 | Human | 119504 | Details Get a Quote |
| ANAPC16 Knockout HeLa Cell Line | EDJ-KQ33002 | Human | 119504 | Details Get a Quote |
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Frequently Asked Questions About anaphase-promoting complex
What is the anaphase-promoting complex (APC/C)?
The anaphase-promoting complex (APC/C) is a multi-subunit E3 ubiquitin ligase that triggers sister chromatid separation and exit from mitosis by degrading mitotic cyclins and anaphase inhibitory proteins.
What genes are involved in the anaphase-promoting complex?
Core subunit genes include ANAPC1-ANAPC11, while coactivators CDC20 and CDH1 (FZR1) and regulators like MAD2L1 and BUB1B modulate its activity.
What is the function of GO:0005680?
GO:0005680 describes the anaphase-promoting complex, a ubiquitin ligase complex that degrades mitotic cyclins and anaphase inhibitory proteins, thereby triggering sister chromatid separation and exit from mitosis.
How is APC/C regulated during mitosis?
APC/C is regulated by coactivator binding (CDC20/CDH1), phosphorylation by CDK1 and PLK1, and inhibition by the spindle assembly checkpoint.
What diseases are associated with APC/C dysfunction?
APC/C dysfunction is linked to cancer, neurodegeneration, and ageing-related pathologies.
What is the D-box motif?
The D-box is a degradation signal originally discovered in cyclin B that is recognized by APC/C to target substrates for ubiquitination.
How can CRISPR be used to study APC/C?
CRISPR knockout, point mutation, knock-in, and overexpression models allow precise dissection of APC/C subunit and substrate functions.
What are the coactivators of APC/C?
CDC20 and CDH1 (FZR1) are the two main coactivators that activate APC/C for distinct substrate sets during different cell cycle phases.
Is APC/C involved in neuronal development?
Yes, APC/C plays critical roles in neuronal differentiation, axon growth, and synapse formation, and its dysregulation is implicated in neurodegeneration.
How does APC/C contribute to ageing?
APC/C is a cellular ageing regulator; its activity declines with age, contributing to protein damage accumulation and genomic instability.
Conclusion
The anaphase-promoting complex (GO:0005680) is a master regulator of mitosis and a versatile E3 ubiquitin ligase with critical roles in cell cycle control, neurobiology, metabolism, and ageing. Its dysfunction is implicated in cancer, neurodegeneration, and age-related diseases, making it a high-priority target for basic and translational research. CRISPR-based models provide powerful tools to dissect APC/C subunit functions and substrate degradation mechanisms, accelerating the development of targeted therapies.
References
- 1. Willems A et al.. 2022. The Plant Anaphase-Promoting Complex/Cyclosome.. Annu Rev Cell Dev Biol 38:25-48 PMID: 35395166
- 2. Liu W et al.. 2023. Lactate regulates cell cycle by remodelling the anaphase promoting complex.. Nature 616(7958):790-797 PMID: 36921622
- 3. Hu X et al.. 2022. The Anaphase-Promoting Complex/Cyclosome Is a Cellular Ageing Regulator.. Int J Mol Sci 23(23) PMID: 36499653
- 4. Curtis NL et al.. 2019. The Anaphase Promoting Complex/Cyclosome (APC/C): A Versatile E3 Ubiquitin Ligase.. Subcell Biochem 93:539-623 PMID: 31939164
- 5. Acquaviva C et al.. 2006. The anaphase-promoting complex/cyclosome: APC/C.. J Cell Sci 119(Pt 12):2401-4 PMID: 16763193
- 6. Kataria M et al.. 2019. Interplay between Phosphatases and the Anaphase-Promoting Complex/Cyclosome in Mitosis.. Cells 8(8) PMID: 31382469
- 7. Schuyler SC et al.. 2024. Suppressing Anaphase-Promoting Complex/Cyclosome-Cell Division Cycle 20 Activity to Enhance the Effectiveness of Anti-Cancer Drugs That Induce Multipolar Mitotic Spindles.. Int J Mol Sci 25(12) PMID: 38928036
- 8. Huang J et al.. 2016. A decade of the anaphase-promoting complex in the nervous system.. Genes Dev 30(6):622-38 PMID: 26980187
