GO:0031145 anaphase-promoting complex-dependent catabolic process: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0031145 describes the ubiquitin-proteasome pathway in which the anaphase-promoting complex/cyclosome (APC/C) catalyzes ubiquitin attachment to target proteins, leading to their degradation.
• APC/C-dependent degradation of cell cycle regulators such as cyclins and securin is essential for mitotic progression and genomic stability.
• The APC/C also targets non-cyclin substrates, including the translesion DNA polymerase REV1 and transcriptional repressors Nrm1 and Yhp1, expanding its role beyond cell cycle control.
• Deregulation of APC/C-dependent proteolysis contributes to cancer and genomic instability, and components such as BubR1 are frequently repressed in acute myeloid leukemia.
• Key experimental approaches to study GO:0031145 include knockout and point-mutation cell models, proteomics, and ubiquitination assays.
• EDITGENE provides CRISPR knockout, point-mutation, knock-in, overexpression cell models and library screening to dissect APC/C-dependent degradation pathways.
Description
The anaphase-promoting complex-dependent catabolic process (GO:0031145) is a conserved ubiquitin-dependent proteolytic pathway that governs the timely destruction of regulatory proteins. The anaphase-promoting complex/cyclosome (APC/C) acts as a multi-subunit E3 ubiquitin ligase that catalyzes the covalent attachment of ubiquitin to specific substrates, marking them for degradation by the 26S proteasome. This process is best known for its role in cell cycle progression, where it triggers the degradation of cyclins and other mitotic regulators to allow exit from mitosis and entry into the next cell cycle phase. Beyond the cell cycle, APC/C-dependent catabolism targets a diverse set of proteins, including the translesion DNA polymerase REV1 and the yeast transcriptional repressors Nrm1 and Yhp1, indicating broader roles in DNA damage tolerance and transcriptional regulation. The specificity of substrate recognition is often mediated by short degradation motifs, such as the destruction box (D-box) or KEN box, and is tightly regulated by co-activators like Cdc20 and Cdh1. For researchers, GO:0031145 represents a paradigm of regulated proteolysis, linking ubiquitin signaling to cell division, genome stability, and disease. Understanding its mechanisms and substrates is critical for developing therapeutic strategies, particularly in cancers where APC/C function is altered.
anaphase-promoting complex-dependent catabolic process At A Glance
| GO ID | GO:0031145 |
|---|---|
| GO term | anaphase-promoting complex-dependent catabolic process |
| Ontology | biological_process |
| Synonym | APC-dependent proteasomal ubiquitin-dependent protein catabolic process; cyclin degradation; cyclin catabolic process |
| Major function | Ubiquitin-mediated proteasomal degradation of cell cycle regulators and other substrates |
| Key enzyme | Anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase |
| Substrate recognition | Mediated by degrons such as the destruction box (D-box) and KEN box |
| Cofactors | Cdc20 and Cdh1 (APC/C activators) |
| Pathway outcome | Targeted protein breakdown, cell cycle progression, genomic stability |
What Is GO:0031145?
GO:0031145, anaphase-promoting complex-dependent catabolic process, is defined as the chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, with ubiquitin-protein ligation catalyzed by the anaphase-promoting complex, and mediated by the proteasome. In simpler terms, it is the APC/C-driven tagging of proteins with ubiquitin, which leads to their destruction by the proteasome.
Why Is anaphase-promoting complex-dependent catabolic process Important in Cell Biology?
GO:0031145 is fundamental to cellular regulation because it ensures the irreversible, timed destruction of proteins that control cell division, DNA repair, and transcription. Dysregulation of this process can lead to genomic instability, aneuploidy, and cancer, making it a critical area of study for understanding tumorigenesis and for developing targeted therapies.
• Controls mitotic progression by degrading cyclins and securin.
• Prevents genomic instability by ensuring proper chromosome segregation.
• Regulates DNA damage tolerance through degradation of REV1.
• Modulates transcription via degradation of repressors like Nrm1 and Yhp1.
• Influences meiotic progression by targeting Spo13.
• Its dysfunction is linked to cancers such as acute myeloid leukemia and colon cancer.
• Provides a model for studying ubiquitin-proteasome system specificity.
• Offers therapeutic targets for antimitotic drugs and cancer treatment.
• Essential for developmental processes and cell differentiation.
• Enables research on protein degradation motifs and co-activator regulation.
What Happens During anaphase-promoting complex-dependent catabolic process?
Substrate Recognition and Binding
In simple terms: The APC/C identifies proteins that need to be destroyed by recognizing short tags on them.
The APC/C recognizes substrates through specific degrons, such as the destruction box (D-box) or KEN box, often in conjunction with co-activators Cdc20 or Cdh1. For example, the meiotic regulator Spo13 contains a novel destruction sequence that targets it for APC/C-dependent degradation during anaphase I. This recognition is highly regulated to ensure timely degradation.
Ubiquitin Conjugation
In simple terms: The APC/C attaches a chain of ubiquitin molecules to the target protein.
Once bound, the APC/C, in collaboration with E2 ubiquitin-conjugating enzymes, catalyzes the covalent attachment of ubiquitin to lysine residues on the substrate. This process is repeated to form a polyubiquitin chain, which serves as a signal for proteasomal degradation. The APC/C itself is a large complex comprising multiple subunits, including catalytic and regulatory components.
Proteasomal Degradation
In simple terms: The tagged protein is recognized and broken down by the proteasome.
The polyubiquitinated substrate is recognized by the 26S proteasome, which unfolds and translocates the protein into its catalytic core, where it is degraded into short peptides. This step is energy-dependent and irreversible, ensuring that the target protein is effectively removed from the cell.
Regulation by Co-activators and Checkpoints
In simple terms: Helper proteins and cell cycle checkpoints control when and where the APC/C is active.
APC/C activity is tightly regulated by its co-activators, Cdc20 and Cdh1, which bind at different stages of the cell cycle and confer substrate specificity. The spindle assembly checkpoint (SAC) inhibits APC/C-Cdc20 until all chromosomes are properly attached to the spindle, preventing premature anaphase onset. Additionally, phosphorylation of APC/C subunits and co-activators modulates its activity.
Diverse Substrates and Biological Outcomes
In simple terms: The APC/C destroys many different proteins, affecting processes beyond cell division.
Beyond cyclins, the APC/C targets proteins such as the translesion DNA polymerase REV1, affecting DNA damage tolerance. In yeast, it degrades transcriptional repressors Nrm1 and Yhp1, linking it to transcriptional regulation. This diversity underscores the broad impact of GO:0031145 on cellular physiology.
Key Genes Involved in GO:0031145 anaphase-promoting complex-dependent catabolic process
The following genes and proteins are central to the anaphase-promoting complex-dependent catabolic process, either as components of the APC/C, co-activators, or well-characterized substrates.
| Gene | Major Role | Research Relevance |
|---|---|---|
| APC/C subunits (e.g., APC1, APC2, APC11) | Core E3 ubiquitin ligase components | Essential for catalytic activity; knockout causes cell cycle arrest |
| CDC20 | Co-activator of APC/C | Required for anaphase initiation; regulates substrate specificity |
| CDH1 (FZR1) | Co-activator of APC/C | Active in G1; targets mitotic cyclins for degradation |
| CCNB1 (Cyclin B) | Substrate | Degradation required for mitotic exit |
| PTTG1 (Securin) | Substrate | Degradation allows separase activation and sister chromatid separation |
| REV1 | Substrate | Degradation by APC/C regulates DNA damage tolerance |
| REV7 | Required for REV1 degradation | Facilitates APC/C-dependent ubiquitination of REV1 |
| NRM1 | Substrate (yeast) | Transcriptional repressor degraded by APC/C |
| YHP1 | Substrate (yeast) | Transcriptional repressor degraded by APC/C |
| SPO13 | Substrate (yeast) | Meiotic regulator degraded in anaphase I |
| BUBR1 (BUB1B) | Mitotic checkpoint kinase | Repressed in AML; re-expression sensitizes to antimitotics |
| CDC20 | Co-activator | Overexpressed in cancers; potential therapeutic target |
| FZR1 | Co-activator | Tumor suppressor role in some contexts |
| ANAPC2 | Core subunit | Mutations linked to genomic instability |
| ANAPC4 | Core subunit | Required for complex assembly |
| ANAPC5 | Core subunit | Scaffold for co-activator binding |
| ANAPC10 | Core subunit | Essential for ubiquitin ligation |
| ANAPC11 | Catalytic subunit | Contains RING domain for E2 recruitment |
How Is anaphase-promoting complex-dependent catabolic process Regulated?
The anaphase-promoting complex-dependent catabolic process is regulated at multiple levels. Co-activators Cdc20 and Cdh1 bind to the APC/C at different cell cycle stages, conferring substrate specificity. Phosphorylation of APC/C subunits and co-activators by cyclin-dependent kinases (CDKs) and other kinases modulates its activity. The spindle assembly checkpoint (SAC) inhibits APC/C-Cdc20 until all chromosomes are properly attached to the mitotic spindle, ensuring genomic integrity. Additionally, deubiquitinating enzymes can reverse ubiquitination, adding another layer of control. In yeast, APC/C-dependent degradation of Nrm1 and Yhp1 is linked to the cell cycle transcriptional program.
anaphase-promoting complex-dependent catabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| BUB1B (BubR1) | Acute myeloid leukemia; mitotic checkpoint defect | Knockout or knockdown in AML cell lines; re-expression via knock-in |
| CDC20 | Various cancers; overexpression linked to poor prognosis | Overexpression and knockout in cancer cell lines |
| REV1 | DNA damage tolerance; chemoresistance | Knockout and point mutation to block APC/C-mediated degradation |
| CCNB1 | Cancer; cell cycle deregulation | Knockout and tagged knock-in for degradation studies |
| PTTG1 | Cancer; chromosomal instability | Knockout and overexpression models |
Cancer and Genomic Instability
Deregulation of APC/C-dependent proteolysis leads to genomic instability, aneuploidy, and cancer. For example, reduced expression of the mitotic checkpoint protein BubR1 is frequently observed in acute myeloid leukemia, and its re-expression sensitizes cells to antimitotic therapy. Bioinformatics analyses have identified APC/C-related genes as prognostic markers in colon cancer.
Acute Myeloid Leukemia
In acute myeloid leukemia, repression of BubR1, a component of the spindle assembly checkpoint that regulates APC/C, contributes to chromosomal instability and poor prognosis. Targeting the APC/C pathway may offer therapeutic opportunities.
Colon Cancer
Screening and verification of key genes with poor prognosis in colon cancer have highlighted the involvement of cell cycle regulators, including APC/C substrates and co-activators. These findings suggest that APC/C-dependent degradation pathways are relevant to colorectal carcinogenesis.
Interstitial Cystitis
Rare variant exome sequencing studies in interstitial cystitis have identified potential associations with genes related to cell cycle regulation, though direct links to APC/C require further investigation.
From anaphase-promoting complex-dependent catabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of APC/C subunit affect cell cycle progression? | CRISPR knockout of ANAPC genes in HeLa or HCT116 cells |
| Does a specific degron mutation stabilize a substrate? | Point mutation of D-box or KEN box in substrate (e.g., cyclin B) |
| Can re-expression of BubR1 restore sensitivity to antimitotics? | Knock-in of BUB1B into AML cells |
| What is the role of REV7 in REV1 degradation? | Knockout of REV7 and overexpression of tagged REV1 |
| How does Cdh1 overexpression affect G1 progression? | Overexpression of CDH1 in cancer cell lines |
| Can APC/C-dependent degradation be monitored in real-time? | Tagged knock-in of substrate with fluorescent reporter |
How to Study the anaphase-promoting complex-dependent catabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| In vitro ubiquitination assay | Ubiquitin chain formation on substrate | Reconstitution of APC/C activity |
| Mass spectrometry proteomics | Protein abundance and ubiquitination sites | Identification of APC/C substrates |
| Live-cell imaging | Degradation kinetics of fluorescent reporters | Real-time monitoring of substrate stability |
| CRISPR knockout screens | Gene essentiality and pathway dependencies | Discovery of regulators of APC/C |
| RNA-seq | Transcriptional changes upon APC/C perturbation | Analysis of downstream effects |
| Co-immunoprecipitation | Protein-protein interactions | Mapping APC/C complex composition |
| Flow cytometry | Cell cycle profiles | Assessing effects of APC/C modulation |
| Yeast genetics | Growth and viability assays | Functional studies of APC/C in S. cerevisiae |
Ubiquitination Assays
In vitro ubiquitination assays using purified APC/C, E1, E2, ubiquitin, and substrate can reconstitute the reaction and measure ubiquitin chain formation. These assays are useful for dissecting the roles of specific subunits and co-activators.
Proteomics and Degradomics
Mass spectrometry-based proteomics can identify APC/C substrates and quantify their degradation over time. Stable isotope labeling by amino acids in cell culture (SILAC) coupled with immunoprecipitation of ubiquitinated proteins can reveal dynamic changes.
Live-Cell Imaging
Fluorescently tagged substrates (e.g., cyclin B-GFP) allow real-time monitoring of degradation kinetics and subcellular localization. This approach is powerful for studying the timing of APC/C activation relative to mitotic events.
Genetic Screens and CRISPR Libraries
Genome-wide CRISPR knockout screens can identify genes required for APC/C-dependent degradation or for resistance to antimitotic drugs. Such screens have uncovered novel regulators and potential therapeutic targets.
How CRISPR Can Be Used to Study GO:0031145 anaphase-promoting complex-dependent catabolic process
Knockout
CRISPR knockout of APC/C subunits or co-activators (e.g., CDC20, CDH1) can abolish APC/C-dependent degradation, leading to cell cycle arrest and accumulation of substrates. Knockout of REV7 stabilizes REV1, confirming its role in degradation.
Point Mutation
Introducing point mutations in degrons (e.g., D-box) of substrates prevents their recognition by APC/C, stabilizing the protein and revealing its function. For example, mutation of the destruction box in Spo13 blocks its degradation in anaphase I.
Knock-in
Knock-in of tagged substrates (e.g., GFP or luciferase) allows tracking of protein stability and localization in live cells. Knock-in of disease-associated variants (e.g., BUB1B mutations) can model their impact on APC/C regulation.
Overexpression
Overexpression of APC/C co-activators or substrates can perturb the stoichiometry of the complex and alter degradation dynamics. For instance, Cdh1 overexpression in G1 can force premature degradation of mitotic cyclins.
How EDITGENE Supports anaphase-promoting complex-dependent catabolic process Research
Researchers studying anaphase-promoting complex-dependent catabolic process-related genes often need to determine whether a candidate gene is causally involved in substrate recognition, ubiquitination, or degradation. EDITGENE provides a comprehensive suite of CRISPR-based services to enable precise genetic manipulation and functional interrogation of this pathway.
Contact EDITGENE today to design your custom CRISPR model for anaphase-promoting complex-dependent catabolic process research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| 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 |
| FBXO31 Knockout HEK293 Cell Line | EDJ-KQ7448 | Human | 79791 | 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 |
| ECRG4 Knockout HEK293 Cell Line | EDJ-KQ10080 | Human | 84417 | 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 |
| 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 |
| ANAPC13 Knockout A-549 Cell Line | EDJ-KQ34198 | Human | 25847 | Details Get a Quote |
| ANAPC13 Knockout HCT 116 Cell Line | EDJ-KQ34199 | Human | 25847 | Details Get a Quote |
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Frequently Asked Questions About anaphase-promoting complex-dependent catabolic process
What is GO:0031145?
GO:0031145 is the Gene Ontology term for anaphase-promoting complex-dependent catabolic process, which describes the ubiquitin-mediated degradation of proteins by the APC/C and proteasome.
What genes are involved in anaphase-promoting complex-dependent catabolic process?
Key genes include APC/C subunits (e.g., ANAPC1-11), co-activators CDC20 and CDH1, and substrates such as CCNB1, PTTG1, and REV1.
How does the anaphase-promoting complex work?
The APC/C is an E3 ubiquitin ligase that binds substrates via degrons, catalyzes ubiquitin chain attachment, and targets them for proteasomal degradation.
What diseases are associated with APC/C dysfunction?
APC/C dysfunction is linked to cancers such as acute myeloid leukemia and colon cancer, as well as genomic instability.
What are the substrates of APC/C?
Substrates include cyclin B, securin, REV1, Spo13, Nrm1, and Yhp1, among others.
How is APC/C activity regulated?
APC/C is regulated by co-activators Cdc20 and Cdh1, phosphorylation, and the spindle assembly checkpoint.
What is the role of REV7 in APC/C-dependent degradation?
REV7 is required for the APC/C-dependent ubiquitination and degradation of the translesion DNA polymerase REV1.
Can CRISPR be used to study APC/C-dependent degradation?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable precise dissection of the pathway.
What methods are used to study GO:0031145?
Common methods include ubiquitination assays, proteomics, live-cell imaging, and CRISPR screens.
Why is APC/C important for cell cycle progression?
APC/C triggers the degradation of cyclins and securin, which is required for mitotic exit and chromosome segregation.
Conclusion
The anaphase-promoting complex-dependent catabolic process (GO:0031145) is a cornerstone of regulated proteolysis, controlling cell cycle progression, DNA damage tolerance, and transcription. Its dysregulation contributes to cancer and genomic instability, making it a prime target for therapeutic intervention. Continued research using advanced CRISPR models and multi-omics approaches will further illuminate its mechanisms and disease relevance.
References
- 1. Wäsch R et al.. 2005. Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells.. Oncogene 24(1):1-10 PMID: 15637585
- 2. Chun AC et al.. 2013. REV7 is required for anaphase-promoting complex-dependent ubiquitination and degradation of translesion DNA polymerase REV1.. Cell Cycle 12(2):365-78 PMID: 23287467
- 3. Ostapenko D et al.. 2011. Anaphase promoting complex-dependent degradation of transcriptional repressors Nrm1 and Yhp1 in Saccharomyces cerevisiae.. Mol Biol Cell 22(13):2175-84 PMID: 21562221
- 4. Sullivan M et al.. 2007. A novel destruction sequence targets the meiotic regulator Spo13 for anaphase-promoting complex-dependent degradation in anaphase I.. J Biol Chem 282(27):19710-5 PMID: 17493939
- 5. Motelow JE et al.. 2026. Interstitial cystitis: a phenotype and rare variant exome sequencing study.. EBioMedicine 125:106150 PMID: 41713163
- 6. Dong B et al.. 2020. Screening and verifying key genes with poor prognosis in colon cancer through bioinformatics analysis.. Transl Cancer Res 9(11):6720-6732 PMID: 35117282
- 7. Motelow JE et al.. 2025. Interstitial Cystitis: a phenotype and rare variant exome sequencing study: Interstitial Cystitis: a phenotype and exome sequencing study.. medRxiv PMID: 40034785
- 8. Schnerch D et al.. 2013. BubR1 is frequently repressed in acute myeloid leukemia and its re-expression sensitizes cells to antimitotic therapy.. Haematologica 98(12):1886-95 PMID: 23812934
