GO:0016235 aggresome: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016235 aggresome is a cellular_component defined as an inclusion body formed by dynein-dependent retrograde transport of an aggregated protein on microtubules.
• Aggresome assembly occurs at the centrosome and requires CP110-CEP97-CEP290 and centriolar satellites.
• Aggresome formation is driven by dynein-dependent retrograde transport of aggregated proteins along microtubules.
• Aggresomes are implicated in neurodegenerative diseases such as Alzheimer's disease and in cancer, including ovarian cancer and hematologic malignancies.
• High-throughput image-based quantification enables aggresome research at scale.
• Aggresome biology can be studied using in silico, in vitro, and ex vivo experiments.
Description
The aggresome (GO:0016235) is a cellular_component defined as an inclusion body formed by dynein-dependent retrograde transport of an aggregated protein on microtubules. It represents a specialized cellular structure that sequesters aggregated proteins, and its formation is a key response to proteotoxic stress. Aggresomes are increasingly recognized as important in both neurodegeneration and cancer, making them a focus of therapeutic and diagnostic research. Understanding aggresome assembly, composition, and regulation is essential for researchers studying protein aggregation, cellular stress responses, and disease mechanisms.
aggresome At A Glance
| GO ID | GO:0016235 |
|---|---|
| GO term | aggresome |
| Ontology | cellular_component |
| Synonym | none |
| Major function | Sequestration of aggregated proteins via dynein-dependent retrograde transport on microtubules |
| Assembly site | Centrosome, driven by CP110-CEP97-CEP290 and centriolar satellites |
| Transport mechanism | Dynein-dependent retrograde transport on microtubules |
| Disease relevance | Neurodegenerative diseases, cancer |
What Is GO:0016235?
The aggresome is a cellular inclusion body that forms when aggregated proteins are transported in a dynein-dependent manner along microtubules to the centrosome, where they accumulate. This process is a cellular response to the accumulation of misfolded or aggregated proteins that cannot be cleared by the proteasome.
Why Is aggresome Important in Cell Biology?
Aggresomes are important because they represent a cellular defense mechanism against proteotoxic stress, and their dysfunction or dysregulation is linked to major human diseases including neurodegenerative disorders and cancer. Studying aggresome biology provides insights into protein quality control, cellular stress responses, and potential therapeutic targets.
• Aggresomes are implicated in neurodegenerative diseases such as Alzheimer's disease.
• Aggresome formation promotes ASK1/JNK signaling activation and stemness maintenance in ovarian cancer.
• The aggresome pathway is a target for therapy in hematologic malignancies.
• Aggresome assembly at the centrosome is driven by CP110-CEP97-CEP290 and centriolar satellites.
• Episodic transport of protein aggregates achieves positive size selectivity in aggresome formation.
• High-throughput image-based aggresome quantification enables drug discovery and screening.
• Aggresome research spans in silico, in vitro, and ex vivo experiments.
• Aggresomes are a key component of the cellular response to proteasome inhibition.
Structure and Composition of aggresome
Centrosomal Assembly and Centriolar Satellites
In simple terms: Aggresomes form at the centrosome, a microtubule-organizing center, with help from specific proteins.
Aggresome assembly occurs at the centrosome and is driven by CP110-CEP97-CEP290 and centriolar satellites. These components are essential for the formation of the aggresome structure.
Dynein-Dependent Retrograde Transport
In simple terms: Aggregated proteins are carried along microtubules toward the centrosome by a motor protein called dynein.
Aggresomes are formed by dynein-dependent retrograde transport of aggregated proteins on microtubules. This transport is a defining feature of aggresome formation.
Size Selectivity in Aggresome Formation
In simple terms: The transport of protein aggregates to the aggresome is selective for larger aggregates.
Episodic transport of protein aggregates achieves a positive size selectivity in aggresome formation. This suggests that the aggresome pathway preferentially handles larger protein aggregates.
Aggresome Composition and Neuropathological Features
In simple terms: Aggresomes contain aggregated proteins and are studied in the context of neurodegenerative diseases.
The neuropathological aggresome has been defined across in silico, in vitro, and ex vivo experiments. Aggresomes are inclusion bodies that accumulate aggregated proteins.
Key Genes Involved in GO:0016235 aggresome
The following genes and proteins are involved in aggresome formation, regulation, and function.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CP110 | Centrosomal protein required for aggresome assembly | Knockout studies to assess aggresome formation |
| CEP97 | Centrosomal protein required for aggresome assembly | Knockout studies to assess aggresome formation |
| CEP290 | Centrosomal protein required for aggresome assembly | Knockout studies to assess aggresome formation |
| Dynein | Motor protein for retrograde transport of aggregates | Inhibition or knockdown to block aggresome formation |
| ASK1 | Kinase activated by aggresome formation in ovarian cancer | Knockout to study signaling and stemness |
| JNK | Kinase activated by aggresome formation in ovarian cancer | Knockout to study signaling and stemness |
| HDAC6 | Histone deacetylase involved in aggresome formation | Inhibition to modulate aggresome pathway |
| SQSTM1/p62 | Autophagy receptor linked to aggresome formation | Knockout to study autophagy-aggresome crosstalk |
| LC3 | Autophagy marker associated with aggresome formation | Knockout to study autophagy-aggresome crosstalk |
| Vimentin | Cytoskeletal protein associated with aggresomes | Knockout to study aggresome structure |
| Ubiquitin | Tag for aggregated proteins targeted to aggresomes | Mutagenesis to study aggresome targeting |
| Proteasome subunits | Proteasome inhibition induces aggresome formation | Knockout to study aggresome induction |
| Centrin | Centrosomal protein associated with aggresomes | Knockout to study centrosomal assembly |
| Pericentrin | Centrosomal protein associated with aggresomes | Knockout to study centrosomal assembly |
| Ninein | Centrosomal protein associated with aggresomes | Knockout to study centrosomal assembly |
| BAG3 | Co-chaperone involved in aggresome formation | Knockout to study aggresome pathway |
| HSP70 | Chaperone involved in aggresome formation | Knockout to study aggresome pathway |
How Is aggresome Regulated?
Aggresome formation is regulated by the autophagy pathway, with autophagy modulation affecting aggresome formation in Alzheimer's disease. Additionally, aggresome formation promotes ASK1/JNK signaling activation in ovarian cancer. The aggresome pathway is also regulated by proteasome inhibition, which induces aggresome formation.
aggresome and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ASK1 | Ovarian cancer stemness | Knockout in ovarian cancer cell lines |
| JNK | Ovarian cancer stemness | Knockout in ovarian cancer cell lines |
| HDAC6 | Neurodegenerative diseases | Knockout in neuronal cell lines |
| SQSTM1/p62 | Alzheimer's disease | Knockout in neuronal cell lines |
| LC3 | Alzheimer's disease | Knockout in neuronal cell lines |
Aggresomes in Neurodegenerative Diseases
Aggresomes are implicated in neurodegenerative diseases such as Alzheimer's disease, where autophagy modulation affects aggresome formation. Aggresome formation and neurodegenerative diseases have therapeutic implications.
Aggresomes in Cancer
Aggresome formation promotes ASK1/JNK signaling activation and stemness maintenance in ovarian cancer. The aggresome pathway is also a target for therapy in hematologic malignancies.
Aggresomes in Protein Aggregation Disorders
Aggresomes are inclusion bodies that form in response to aggregated proteins, and their neuropathological features have been defined across experimental models. They are a key component of the cellular response to proteotoxic stress.
From aggresome-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CP110 knockout disrupt aggresome assembly? | CP110 knockout cell line |
| Does CEP97 knockout disrupt aggresome assembly? | CEP97 knockout cell line |
| Does CEP290 knockout disrupt aggresome assembly? | CEP290 knockout cell line |
| Does ASK1 knockout affect ovarian cancer stemness? | ASK1 knockout ovarian cancer cell line |
| Does JNK knockout affect ovarian cancer stemness? | JNK knockout ovarian cancer cell line |
| Does HDAC6 inhibition affect aggresome formation? | HDAC6 knockout or inhibitor-treated cells |
How to Study the aggresome Process
| Method | What It Measures | Typical Application |
|---|---|---|
| High-throughput imaging | Aggresome quantification | Drug screening |
| In silico modeling | Aggresome structure and dynamics | Neuropathological aggresome definition |
| In vitro assays | Aggresome formation | Mechanistic studies |
| Ex vivo experiments | Aggresome in tissue | Neuropathology |
| Autophagy modulation | Aggresome formation | Alzheimer's disease research |
| Transport assays | Size selectivity | Aggresome formation mechanism |
| Proteasome inhibition | Aggresome induction | Protein aggregation studies |
High-Throughput Image-Based Aggresome Quantification
High-throughput image-based aggresome quantification allows for automated measurement of aggresome formation in cells. This method is useful for screening compounds that modulate aggresome formation.
In Silico, In Vitro, and Ex Vivo Experiments
Aggresome research spans in silico, in vitro, and ex vivo experiments to define neuropathological aggresomes. These complementary approaches provide a comprehensive understanding of aggresome biology.
Autophagy Modulation Studies
Autophagy modulation can be used to study aggresome formation in the context of Alzheimer's disease. This involves manipulating autophagy pathways and measuring aggresome formation.
Transport and Size Selectivity Assays
Episodic transport of protein aggregates can be studied to understand size selectivity in aggresome formation. This involves tracking the movement of aggregates along microtubules.
How CRISPR Can Be Used to Study GO:0016235 aggresome
Knockout
CRISPR knockout of CP110, CEP97, or CEP290 can be used to assess their requirement for aggresome assembly at the centrosome. Knockout of ASK1 or JNK can be used to study aggresome-mediated signaling in ovarian cancer.
Point Mutation
Point mutations can be introduced into genes such as HDAC6 or SQSTM1/p62 to study their role in aggresome formation and autophagy crosstalk.
Knock-in
Knock-in of tagged versions of aggresome components, such as CP110 or CEP290, can enable live-cell imaging of aggresome assembly.
Overexpression
Overexpression of aggregation-prone proteins can induce aggresome formation and be used to study the aggresome pathway.
How EDITGENE Supports aggresome Research
Researchers studying aggresome-related genes often need to determine whether a candidate gene is causally involved in aggresome formation, regulation, or disease. EDITGENE provides CRISPR-based services to enable these studies.
Contact EDITGENE today to design your custom CRISPR model for aggresome research.
Frequently Asked Questions About aggresome
What is the aggresome GO:0016235?
The aggresome (GO:0016235) is a cellular_component defined as an inclusion body formed by dynein-dependent retrograde transport of an aggregated protein on microtubules.
What genes are involved in aggresome formation?
Genes involved include CP110, CEP97, CEP290, dynein, ASK1, JNK, HDAC6, SQSTM1/p62, LC3, and others.
Where does aggresome assembly occur?
Aggresome assembly occurs at the centrosome and is driven by CP110-CEP97-CEP290 and centriolar satellites.
How is aggresome formation regulated?
Aggresome formation is regulated by autophagy modulation and proteasome inhibition, and it promotes ASK1/JNK signaling in ovarian cancer.
What diseases are associated with aggresomes?
Aggresomes are associated with neurodegenerative diseases such as Alzheimer's disease and cancers including ovarian cancer and hematologic malignancies.
How can aggresomes be quantified?
Aggresomes can be quantified using high-throughput image-based methods.
What is the role of dynein in aggresome formation?
Dynein mediates retrograde transport of aggregated proteins on microtubules to form aggresomes.
What is the size selectivity in aggresome formation?
Episodic transport of protein aggregates achieves a positive size selectivity in aggresome formation.
What model systems are used to study aggresomes?
In silico, in vitro, and ex vivo experiments are used to define neuropathological aggresomes.
How can CRISPR be used to study aggresomes?
CRISPR knockout, point mutation, knock-in, and overexpression can be used to study aggresome-related genes.
Conclusion
The aggresome (GO:0016235) is a critical cellular_component involved in the sequestration of aggregated proteins via dynein-dependent retrograde transport on microtubules. Its assembly at the centrosome requires CP110-CEP97-CEP290 and centriolar satellites. Aggresomes are implicated in neurodegenerative diseases and cancer, making them important targets for research and therapy. Continued research using advanced methods such as high-throughput imaging and CRISPR models will further elucidate aggresome biology.
References
- 1. Prosser SL et al.. 2022. Aggresome assembly at the centrosome is driven by CP110-CEP97-CEP290 and centriolar satellites.. Nat Cell Biol 24(4):483-496 PMID: 35411088
- 2. Chen Y et al.. 2024. Aggresome formation promotes ASK1/JNK signaling activation and stemness maintenance in ovarian cancer.. Nat Commun 15(1):1321 PMID: 38351029
- 3. Olzmann JA et al.. 2008. Aggresome formation and neurodegenerative diseases: therapeutic implications.. Curr Med Chem 15(1):47-60 PMID: 18220762
- 4. Rahman MA et al.. 2022. Autophagy Modulation in Aggresome Formation: Emerging Implications and Treatments of Alzheimer's Disease.. Biomedicines 10(5) PMID: 35625764
- 5. Lesire L et al.. 2020. High-Throughput Image-Based Aggresome Quantification.. SLAS Discov 25(7):783-791 PMID: 32449635
- 6. Fang R et al.. 2025. Episodic transport of protein aggregates achieves a positive size selectivity in aggresome formation.. Nat Commun 16(1):7852 PMID: 40846843
- 7. Gomes GN et al.. 2021. Defining the Neuropathological Aggresome across in Silico, in Vitro, and ex Vivo Experiments.. J Phys Chem B 125(8):1974-1996 PMID: 33464098
- 8. Simms-Waldrip T et al.. 2008. The aggresome pathway as a target for therapy in hematologic malignancies.. Mol Genet Metab 94(3):283-6 PMID: 18472289
