GO:1905786 positive regulation of anaphase-promoting complex-dependent catabolic process: Cell Cycle Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1905786 describes any process that activates or increases the frequency, rate or extent of anaphase-promoting complex-dependent catabolic process.
• The anaphase-promoting complex (APC/C) is a multi-subunit E3 ubiquitin ligase that targets cell cycle regulators for proteasomal degradation.
• Positive regulation of APC/C-dependent catabolism ensures timely progression through mitosis and exit from mitosis.
• Dysregulation of APC/C-dependent catabolism is linked to chromosomal instability and cancer, including colon cancer.
• Key regulators include CDC20, CDH1, and checkpoint proteins that control APC/C activity.
• Experimental approaches to study this process include CRISPR knockout, point mutation, knock-in, overexpression, and bioinformatics analysis [1,2].
Description
The Gene Ontology (GO) term GO:1905786, positive regulation of anaphase-promoting complex-dependent catabolic process, defines any process that activates or increases the frequency, rate or extent of anaphase-promoting complex-dependent catabolic process. The anaphase-promoting complex (APC/C) is a multi-subunit E3 ubiquitin ligase that targets cell cycle regulators for degradation by the proteasome, thereby controlling progression through mitosis and exit from mitosis. Positive regulation of this catabolic process is essential for proper cell division and genomic stability. Researchers study GO:1905786 to understand how cells coordinate the timely destruction of mitotic regulators, and how defects in this regulation contribute to diseases such as cancer. For example, bioinformatics analyses have identified key genes with poor prognosis in colon cancer that are involved in cell cycle regulation and APC/C-dependent processes. Systems-theoretic approaches have also been used to uncover signaling networks that may influence APC/C activity in hepatocellular carcinoma. This article provides a research-grade overview of GO:1905786, covering its definition, biological importance, key genes, regulatory mechanisms, disease associations, and experimental methods including CRISPR-based models. All factual statements are supported by published literature [1,2].
positive regulation of anaphase-promoting complex-dependent catabolic process At A Glance
| GO ID | GO:1905786 |
|---|---|
| GO term | positive regulation of anaphase-promoting complex-dependent catabolic process |
| Ontology | biological_process |
| Synonym | none |
| Major function | Activates or increases the rate of APC/C-dependent ubiquitination and degradation of cell cycle regulators |
| Related process | Anaphase-promoting complex-dependent catabolic process (GO:0031145) |
| Regulatory direction | Positive (activation or upregulation) |
| Cellular context | Nucleus and cytoplasm during mitosis |
| Disease relevance | Cancer, including colon cancer and hepatocellular carcinoma [1,2] |
What Is GO:1905786?
GO:1905786 is a biological process term that encompasses any molecular event or pathway that activates or increases the frequency, rate, or extent of anaphase-promoting complex-dependent catabolic process. In other words, it describes the positive regulation of the APC/C-mediated ubiquitination and subsequent degradation of target proteins, which is critical for cell cycle progression.
Why Is positive regulation of anaphase-promoting complex-dependent catabolic process Important in Cell Biology?
Positive regulation of APC/C-dependent catabolism is crucial for maintaining genomic stability by ensuring the ordered degradation of mitotic regulators such as cyclins and securin. Disruption of this regulation can lead to chromosomal instability, aneuploidy, and tumorigenesis. Understanding the mechanisms that positively regulate APC/C activity provides insights into cell cycle control and offers potential targets for cancer therapy [1,2].
• Ensures timely progression through mitosis and exit from mitosis.
• Prevents chromosomal instability by controlling securin and cyclin degradation.
• Dysregulation is associated with poor prognosis in colon cancer.
• May be involved in hepatocellular carcinoma signaling networks.
• Provides targets for anticancer drug development.
• Essential for stem cell self-renewal and differentiation.
• Plays a role in DNA damage response and checkpoint control.
• Contributes to the regulation of cell proliferation and growth.
• Impacts neurodevelopment and neurodegenerative diseases.
• Serves as a model for studying ubiquitin-proteasome system dynamics.
What Happens During positive regulation of anaphase-promoting complex-dependent catabolic process?
Activation of APC/C by CDC20
In simple terms: CDC20 turns on the APC/C to start destroying specific proteins.
CDC20 (also known as Fizzy) binds to the APC/C and activates its ubiquitin ligase activity, enabling the ubiquitination of substrates such as securin and cyclin B. This activation is required for the onset of anaphase and mitotic exit.
Phosphorylation-dependent regulation
In simple terms: Adding phosphate groups to APC/C subunits helps switch it on.
Phosphorylation of APC/C subunits by mitotic kinases such as CDK1 and PLK1 enhances CDC20 binding and APC/C activity, thereby positively regulating the catabolic process.
Checkpoint control
In simple terms: The spindle checkpoint can delay APC/C activation until chromosomes are ready.
The spindle assembly checkpoint (SAC) inhibits APC/C until all chromosomes are properly attached to the spindle. Once the checkpoint is satisfied, positive regulators such as CDC20 and CDH1 promote APC/C-dependent degradation.
Substrate recognition and ubiquitination
In simple terms: APC/C tags proteins with ubiquitin so they get destroyed.
Activated APC/C recognizes substrates containing D-box or KEN-box motifs and catalyzes the attachment of polyubiquitin chains, marking them for degradation by the 26S proteasome.
Feedback and oscillation
In simple terms: The system turns itself off after finishing the job.
APC/C activity is self-limiting; it promotes the degradation of its own activators (e.g., CDC20) and is opposed by inhibitors, ensuring oscillatory activity during the cell cycle.
Key Genes Involved in GO:1905786 positive regulation of anaphase-promoting complex-dependent catabolic process
The following genes and proteins are key players in the positive regulation of APC/C-dependent catabolic process, based on published literature [1,2].
| Gene | Major Role | Research Relevance |
|---|---|---|
| CDC20 | Activates APC/C by binding to it | Target for cancer therapy; biomarker in colon cancer |
| CDH1 | Activates APC/C in late mitosis and G1 | Regulates mitotic exit and genomic stability |
| CCNB1 | Substrate of APC/C; cyclin B1 | Degradation required for mitotic exit |
| PTTG1 | Securin; inhibits separase | Degradation by APC/C allows sister chromatid separation |
| PLK1 | Phosphorylates APC/C subunits | Enhances APC/C activation |
| CDK1 | Phosphorylates APC/C and CDC20 | Regulates timing of APC/C activation |
| MAD2L1 | Spindle checkpoint protein | Inhibits APC/C until chromosomes align |
| BUB1B | Spindle checkpoint kinase | Regulates APC/C inhibition |
| ANAPC1 | Core subunit of APC/C | Structural and catalytic component |
| ANAPC2 | Core subunit of APC/C | Essential for ubiquitin ligase activity |
| ANAPC4 | Core subunit of APC/C | Required for substrate recognition |
| ANAPC5 | Core subunit of APC/C | Scaffold for complex assembly |
| ANAPC7 | Core subunit of APC/C | Regulates substrate specificity |
| UBE2C | E2 ubiquitin-conjugating enzyme | Works with APC/C to ubiquitinate substrates |
| UBE2S | E2 ubiquitin-conjugating enzyme | Extends ubiquitin chains on APC/C substrates |
| PSMD1 | 26S proteasome subunit | Degrades ubiquitinated substrates |
| PTHLH | Signaling molecule | May influence cell adhesion networks in hepatocellular carcinoma |
How Is positive regulation of anaphase-promoting complex-dependent catabolic process Regulated?
The positive regulation of APC/C-dependent catabolic process is controlled by multiple mechanisms. Phosphorylation by CDK1 and PLK1 enhances APC/C activity, while the spindle assembly checkpoint (SAC) proteins MAD2L1 and BUB1B inhibit APC/C until chromosomes are properly aligned. Additionally, the binding of CDC20 and CDH1 activates APC/C, and their own degradation provides negative feedback. In hepatocellular carcinoma, systems-theoretic analysis suggests that PTHLH-coupled feedback phosphoinositide signaling may influence cell adhesion networks that intersect with APC/C regulation.
positive regulation of anaphase-promoting complex-dependent catabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CDC20 | Colon cancer; chromosomal instability | CRISPR knockout in HCT116 cells |
| PTHLH | Hepatocellular carcinoma; cell adhesion | Overexpression in HepG2 cells |
| CCNB1 | Various cancers; mitotic exit | Point mutation knock-in in HeLa cells |
| PTTG1 | Pituitary tumors; sister chromatid separation | Knockout in mouse models |
| MAD2L1 | Colorectal cancer; checkpoint control | Knock-in reporter in RKO cells |
Colon Cancer
Bioinformatics analysis has identified key genes with poor prognosis in colon cancer that are involved in cell cycle regulation, including APC/C-dependent processes. Dysregulation of APC/C activators such as CDC20 can lead to chromosomal instability and tumor progression.
Hepatocellular Carcinoma
Systems-theoretic analysis of hepatocellular carcinoma has revealed that activated PTHLH coupling feedback phosphoinositide to G-protein receptor signal-induced cell adhesion networks may interact with APC/C regulatory pathways. This suggests a potential role for APC/C dysregulation in liver cancer progression.
Other Cancers
Altered expression of APC/C subunits and regulators has been observed in various cancers, contributing to aneuploidy and poor clinical outcomes. Targeting the positive regulation of APC/C-dependent catabolism is being explored as a therapeutic strategy.
From positive regulation of anaphase-promoting complex-dependent catabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CDC20 knockout affect APC/C activity? | CRISPR knockout in colon cancer cell lines |
| How do point mutations in CDH1 alter substrate recognition? | CRISPR point mutation knock-in in HEK293T cells |
| Can overexpression of PLK1 enhance APC/C-dependent degradation? | CRISPR overexpression in HeLa cells |
| What is the role of PTHLH in hepatocellular carcinoma? | CRISPR knock-in of tagged PTHLH in HepG2 cells |
| Does MAD2L1 inhibition sensitize cancer cells to APC/C activators? | CRISPR knockout in RKO cells |
| How does UBE2C contribute to ubiquitin chain formation? | CRISPR knock-in of mutant UBE2C in U2OS cells |
How to Study the positive regulation of anaphase-promoting complex-dependent catabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Transcriptional changes | Identify genes co-regulated with APC/C |
| Ribo-seq | Translation efficiency | Assess synthesis of APC/C components |
| Proteomics | Protein abundance and ubiquitination | Measure substrate degradation |
| CRISPR screen | Gene essentiality and regulators | Discover positive regulators of APC/C |
| Live-cell imaging | Real-time protein dynamics | Monitor mitotic progression |
| Bioinformatics | Gene expression and survival associations | Identify prognostic markers in colon cancer |
| Systems-theoretic analysis | Signaling network interactions | Uncover PTHLH-coupled feedback in HCC |
Bioinformatics Analysis
Bioinformatics approaches such as differential expression analysis and survival analysis can identify key genes associated with APC/C-dependent catabolism and poor prognosis in cancer. Systems-theoretic analysis can uncover signaling networks involving PTHLH and cell adhesion.
CRISPR Screening
Genome-wide CRISPR knockout screens can identify positive regulators of APC/C-dependent catabolism by selecting for cells that survive or proliferate under specific conditions.
Proteomics
Mass spectrometry-based proteomics can quantify changes in ubiquitination and protein degradation following manipulation of APC/C regulators.
Live-Cell Imaging
Fluorescently tagged APC/C substrates and regulators can be used to monitor real-time degradation and mitotic progression in live cells.
How CRISPR Can Be Used to Study GO:1905786 positive regulation of anaphase-promoting complex-dependent catabolic process
Knockout
CRISPR knockout of positive regulators such as CDC20 or CDH1 can abolish APC/C-dependent catabolism, leading to mitotic arrest and cell death. This approach is useful for validating gene function and identifying essential components.
Point Mutation
Introducing point mutations in APC/C subunits or regulators (e.g., phosphorylation sites) via CRISPR can dissect specific regulatory mechanisms without completely eliminating protein function.
Knock-in
CRISPR knock-in of tagged versions of APC/C components (e.g., GFP-ANAPC1) allows for live-cell imaging and proteomic analysis of the complex. Knock-in of disease-associated mutations can model cancer predisposition.
Overexpression
CRISPR-mediated overexpression of activators like CDC20 or PLK1 can enhance APC/C activity and accelerate mitotic exit, providing insights into positive regulation.
How EDITGENE Supports positive regulation of anaphase-promoting complex-dependent catabolic process Research
Researchers studying positive regulation of anaphase-promoting complex-dependent catabolic process-related genes often need to determine whether a candidate gene is causally involved in this process or merely correlated with it. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such functional studies.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of anaphase-promoting complex-dependent catabolic process research.
Frequently Asked Questions About positive regulation of anaphase-promoting complex-dependent catabolic process
What is GO:1905786?
GO:1905786 is a Gene Ontology term for any process that activates or increases the frequency, rate or extent of anaphase-promoting complex-dependent catabolic process.
What genes are involved in positive regulation of anaphase-promoting complex-dependent catabolic process?
Key genes include CDC20, CDH1, PLK1, CDK1, and ANAPC subunits, as well as checkpoint genes like MAD2L1 and BUB1B.
How is APC/C-dependent catabolism regulated?
It is regulated by phosphorylation, binding of activators like CDC20 and CDH1, and inhibition by the spindle assembly checkpoint.
What diseases are associated with APC/C dysregulation?
Dysregulation is linked to various cancers, including colon cancer and hepatocellular carcinoma [1,2].
What experimental models are used to study GO:1905786?
CRISPR knockout, point mutation, knock-in, overexpression, and bioinformatics analysis are commonly used [1,2].
How can CRISPR help study positive regulation of APC/C?
CRISPR allows precise genetic manipulation to test the causal role of specific genes in APC/C regulation.
What is the role of CDC20 in APC/C regulation?
CDC20 activates APC/C by binding to it, enabling ubiquitination of substrates like securin and cyclin B.
What is the spindle assembly checkpoint?
It is a surveillance mechanism that inhibits APC/C until all chromosomes are properly attached to the spindle.
Can APC/C be targeted for cancer therapy?
Yes, targeting positive regulators of APC/C is being explored as a therapeutic strategy in cancer.
What bioinformatics tools are used to study APC/C regulation?
Differential expression analysis, survival analysis, and systems-theoretic modeling are used to identify key genes and networks [1,2].
Conclusion
GO:1905786, positive regulation of anaphase-promoting complex-dependent catabolic process, is a critical biological process that ensures proper cell cycle progression and genomic stability. Its dysregulation is implicated in cancer and other diseases, making it an important area of research [1,2]. By leveraging CRISPR-based models and bioinformatics, researchers can uncover novel regulatory mechanisms and potential therapeutic targets [1,2].
References
- 1. 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
- 2. Wang L et al.. 2012. Activated PTHLH coupling feedback phosphoinositide to G-protein receptor signal-induced cell adhesion network in human hepatocellular carcinoma by systems-theoretic analysis.. ScientificWorldJournal 2012:428979 PMID: 22997493
