GO:0035853 chromosome passenger complex localization to spindle midzone: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0035853 describes the process by which the chromosome passenger complex (CPC) is transported to or maintained at the spindle midzone during mitosis.
• The CPC consists of Aurora B kinase, INCENP, Survivin (BIRC5), and Borealin (CDCA8), and its midzone localization is essential for cytokinesis and chromosome segregation.
• Midzone localization of the CPC is negatively regulated by Cdk1 phosphorylation of the kinesin Mklp2, which prevents premature CPC accumulation at the midzone.
• The Nup107-160 nucleoporin complex and INCENP-Aurora B interactions modulate CPC localization and kinase activity.
• Disruption of CPC midzone localization leads to cytokinesis failure, aneuploidy, and has been linked to cancer and developmental disorders.
• Research tools such as live-cell imaging, CRISPR knockout, and knock-in tagging are used to study CPC dynamics and function.
Description
The chromosome passenger complex (CPC) is a conserved protein complex that orchestrates key mitotic events, including chromosome alignment, spindle assembly checkpoint, and cytokinesis. Its dynamic localization to distinct mitotic structures is critical for its functions. GO:0035853, chromosome passenger complex localization to spindle midzone, is a biological process that ensures the CPC is transported to or maintained at the spindle midzone, the region where antiparallel microtubules overlap. This process is essential for proper cytokinesis and genomic stability. Understanding the molecular mechanisms governing CPC midzone localization is crucial for researchers studying cell division, cancer, and developmental biology.
chromosome passenger complex localization to spindle midzone At A Glance
| GO ID | GO:0035853 |
|---|---|
| GO term | chromosome passenger complex localization to spindle midzone |
| Ontology | biological_process |
| Synonym | CPC localization to spindle midzone; chromosomal passenger complex localization to central spindle; CPC complex localization to spindle equator |
| Major function | Transport or maintenance of the CPC at the spindle midzone during mitosis |
| Complex components | Aurora B kinase, INCENP, Survivin (BIRC5), Borealin (CDCA8) |
| Regulation | Negatively regulated by Cdk1-mediated phosphorylation of Mklp2 |
| Disease relevance | Cytokinesis failure, aneuploidy, cancer |
What Is GO:0035853?
GO:0035853 is a biological process term defined as the cellular protein complex localization that results in the chromosome passenger complex being transported to or maintained at the spindle midzone. The chromosome passenger complex contains Survivin (BIRC5), Aurora B kinase, INCENP, and Borealin (CDCA8), and coordinates various mitotic events based on its location. The spindle midzone is the central region of the spindle where microtubules from opposite poles overlap.
Why Is chromosome passenger complex localization to spindle midzone Important in Cell Biology?
Proper localization of the chromosome passenger complex to the spindle midzone is essential for cytokinesis, the final step of cell division. Failure of this process results in binucleation or aneuploidy, which can drive tumorigenesis and developmental defects. Therefore, understanding GO:0035853 provides insights into fundamental cell biology and potential therapeutic targets in cancer and other proliferative diseases.
• Ensures accurate chromosome segregation and cytokinesis.
• Prevents aneuploidy and genomic instability.
• Regulates RhoA signaling for contractile ring formation.
• Dysregulation is linked to cancer progression.
• Required for proper spindle midzone organization.
• Target of Cdk1 regulation for mitotic timing.
• Involves nucleoporin complex for localization.
• Conserved from yeast to humans, with variations in trypanosomes.
• Key for understanding cytokinesis failure in disease.
• Potential target for anti-cancer therapies.
What Happens During chromosome passenger complex localization to spindle midzone?
Initiation and Transport
In simple terms: The CPC is moved to the center of the mitotic spindle by motor proteins and other factors.
During anaphase, the CPC is transported from centromeres to the spindle midzone. This process requires the kinesin Mklp2, which binds to the CPC and moves along microtubules. Cdk1 phosphorylates Mklp2 to inhibit premature midzone localization until anaphase onset.
Maintenance at the Midzone
In simple terms: Once at the midzone, the CPC is kept there by interactions with other proteins and microtubules.
The CPC is maintained at the spindle midzone through interactions with microtubules and other proteins such as the Nup107-160 nucleoporin complex. INCENP-Aurora B interactions modulate kinase activity and CPC localization.
Role in Cytokinesis
In simple terms: At the midzone, the CPC signals for the cell to divide.
At the spindle midzone, Aurora B kinase phosphorylates substrates such as Mklp1 and RhoA regulators to promote contractile ring formation and abscission. This ensures proper cytokinesis and cell separation.
Regulation by Cdk1
In simple terms: A master kinase, Cdk1, controls when the CPC moves to the midzone.
Cdk1 negatively regulates midzone localization of Mklp2 and the CPC by phosphorylation. Dephosphorylation by Cdc14 at anaphase triggers their relocation to the midzone.
Key Genes Involved in GO:0035853 chromosome passenger complex localization to spindle midzone
The following genes and proteins are key players in chromosome passenger complex localization to spindle midzone.
| Gene | Major Role | Research Relevance |
|---|---|---|
| AURKB | Aurora B kinase, catalytic subunit of CPC | Phosphorylates substrates at midzone; target for cancer therapy |
| INCENP | Scaffold protein of CPC, activates Aurora B | Modulates kinase activity and localization |
| BIRC5 | Survivin, regulatory subunit of CPC | Inhibits apoptosis, regulates CPC localization |
| CDCA8 | Borealin, regulatory subunit of CPC | Required for CPC targeting to centromeres and midzone |
| KIF20A | Mklp2, kinesin motor | Transports CPC to midzone; regulated by Cdk1 |
| KIF23 | Mklp1, kinesin motor | Essential for cytokinesis; phosphorylated by Aurora B |
| NUP107 | Nucleoporin, part of Nup107-160 complex | Promotes CPC localization to midzone |
| NUP160 | Nucleoporin, part of Nup107-160 complex | Promotes CPC localization to midzone |
| CDK1 | Cyclin-dependent kinase 1 | Phosphorylates Mklp2 to inhibit premature CPC localization |
| CDC14A | Phosphatase | Dephosphorylates Mklp2 to allow CPC midzone localization |
| RHOА | RhoA GTPase | Regulates contractile ring; downstream of CPC |
| ANLN | Anillin | Binds to CPC and regulates cytokinesis |
| PLK1 | Polo-like kinase 1 | Regulates CPC localization and cytokinesis |
| TPX2 | Microtubule-associated protein | Regulates spindle assembly and CPC localization |
| KIF4A | Kinesin motor | Regulates midzone organization and CPC |
| PRC1 | Protein regulator of cytokinesis 1 | Organizes midzone microtubules |
| ECT2 | RhoA guanine nucleotide exchange factor | Activated by CPC for cytokinesis |
| KIN-A | Orphan kinesin in trypanosomes | Controls CPC localization in trypanosomes |
How Is chromosome passenger complex localization to spindle midzone Regulated?
The localization of the chromosome passenger complex to the spindle midzone is regulated by phosphorylation. Cdk1 phosphorylates the kinesin Mklp2, preventing its interaction with the CPC and inhibiting premature midzone localization during metaphase. At anaphase onset, Cdk1 activity decreases, and the phosphatase Cdc14 dephosphorylates Mklp2, allowing CPC transport to the midzone. Additionally, the Nup107-160 nucleoporin complex promotes CPC localization by controlling its localization state. INCENP-Aurora B interactions also modulate kinase activity and CPC localization.
chromosome passenger complex localization to spindle midzone and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| AURKB | Cancer, chromosomal instability | Knockout or point mutation in cancer cell lines |
| BIRC5 | Cancer, apoptosis resistance | Overexpression in HeLa cells |
| CDCA8 | Developmental disorders, cytokinesis failure | Knockout in zebrafish or mouse models |
| KIF20A | Cancer, mitotic defects | Knockdown in U2OS cells |
| NUP107 | Nephrotic syndrome, mitotic defects | Knockout in podocytes |
Cancer
Dysregulation of CPC localization and Aurora B kinase activity is associated with various cancers. Overexpression of Aurora B and Survivin leads to chromosomal instability and tumor progression. Targeting CPC components is a therapeutic strategy in clinical trials.
Developmental Disorders
Mutations in CPC genes can cause developmental defects due to cytokinesis failure. For example, mutations in CDCA8 or AURKB may lead to microcephaly or other congenital anomalies.
Trypanosomiasis
In Trypanosoma brucei, the CPC localization is controlled by orphan kinesins KIN-A and KIN-B, which are essential for cytokinesis. Disruption leads to cell division defects, highlighting potential drug targets.
From chromosome passenger complex localization to spindle midzone-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| What is the role of Aurora B in CPC midzone localization? | Knockout of AURKB in HeLa cells |
| How does Cdk1 phosphorylation regulate Mklp2? | Point mutation of Cdk1 sites in KIF20A |
| Where does the CPC localize in live cells? | Knock-in of fluorescent tags (e.g., GFP) into INCENP |
| What happens when CPC is overexpressed? | Overexpression of BIRC5 in cancer cells |
| How does Nup107-160 complex affect CPC? | Knockout of NUP107 in HeLa cells |
| What is the role of KIN-A in trypanosomes? | Knockout of KIN-A in T. brucei |
How to Study the chromosome passenger complex localization to spindle midzone Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Dynamic localization of CPC | Visualize CPC movement to midzone |
| CRISPR knockout | Loss-of-function effects | Study gene requirement for CPC localization |
| Co-immunoprecipitation | Protein-protein interactions | Identify CPC partners |
| Phospho-specific Western blot | Phosphorylation status | Measure Cdk1 and Aurora B activity |
| RNAi knockdown | Gene silencing | Transient depletion of CPC components |
| Fluorescence resonance energy transfer (FRET) | Kinase activity in live cells | Monitor Aurora B activity at midzone |
| Electron microscopy | Ultrastructure of midzone | Visualize microtubule organization |
Live-Cell Imaging
Fluorescently tagged CPC components (e.g., GFP-Aurora B) allow real-time visualization of CPC dynamics during mitosis. This method reveals the timing and spatial regulation of midzone localization.
CRISPR/Cas9 Genome Editing
Knockout or knock-in of CPC genes using CRISPR enables functional studies. For example, knockout of AURKB abolishes CPC midzone localization and causes cytokinesis failure.
Proteomics and Co-Immunoprecipitation
Mass spectrometry and co-IP identify interacting partners of CPC at the midzone, such as Mklp2 and Nup107-160 complex.
Phosphorylation Assays
In vitro kinase assays and phospho-specific antibodies measure Aurora B activity and Cdk1-mediated phosphorylation of Mklp2.
How CRISPR Can Be Used to Study GO:0035853 chromosome passenger complex localization to spindle midzone
Knockout
CRISPR knockout of CPC genes (e.g., AURKB, INCENP) results in loss of midzone localization and cytokinesis failure, providing causal evidence for their role in GO:0035853.
Point Mutation
Introducing point mutations in phosphorylation sites (e.g., KIF20A) can test the role of Cdk1 regulation in CPC localization.
Knock-in
Knock-in of fluorescent tags (e.g., GFP) into endogenous CPC genes allows tracking of the complex in live cells without overexpression artifacts.
Overexpression
Overexpression of CPC components (e.g., BIRC5) can mimic cancer-associated states and reveal effects on midzone localization and cytokinesis.
How EDITGENE Supports chromosome passenger complex localization to spindle midzone Research
Researchers studying chromosome passenger complex localization to spindle midzone-related genes often need to determine whether a candidate gene is causally involved in the process or merely correlated. EDITGENE provides a comprehensive suite of CRISPR services to enable such functional studies.
Contact EDITGENE today to design your custom CRISPR model for chromosome passenger complex localization to spindle midzone research.
Frequently Asked Questions About chromosome passenger complex localization to spindle midzone
What is chromosome passenger complex localization to spindle midzone?
It is the process by which the CPC is transported to or maintained at the spindle midzone during mitosis, essential for cytokinesis.
What genes are involved in chromosome passenger complex localization to spindle midzone?
Key genes include AURKB, INCENP, BIRC5, CDCA8, KIF20A, and NUP107.
How is CPC localization regulated?
It is regulated by Cdk1 phosphorylation of Mklp2 and dephosphorylation by Cdc14.
What diseases are associated with defects in CPC localization?
Cancer, developmental disorders, and trypanosomiasis.
What methods are used to study CPC localization?
Live-cell imaging, CRISPR knockout, co-IP, and phosphorylation assays.
What is the role of Aurora B in CPC localization?
Aurora B is the catalytic subunit; its activity and interactions with INCENP modulate CPC localization.
How does Cdk1 regulate CPC midzone localization?
Cdk1 phosphorylates Mklp2 to inhibit premature CPC localization until anaphase.
What is the spindle midzone?
The central region of the mitotic spindle where antiparallel microtubules overlap.
Can CRISPR be used to study CPC localization?
Yes, knockout, knock-in, and point mutations enable functional studies.
What happens if CPC fails to localize to the midzone?
Cytokinesis failure, aneuploidy, and genomic instability.
Conclusion
GO:0035853, chromosome passenger complex localization to spindle midzone, is a critical biological process for accurate cell division. Its regulation by Cdk1 and interactions with motor proteins and nucleoporins ensure timely CPC relocation. Dysregulation leads to cancer and developmental defects, making it a valuable research and therapeutic target. EDITGENE offers advanced CRISPR tools to dissect this process.
References
- 1. Hornick JE et al.. 2010. Kinesins to the core: The role of microtubule-based motor proteins in building the mitotic spindle midzone.. Semin Cell Dev Biol 21(3):290-9 PMID: 20109573
- 2. Hümmer S et al.. 2009. Cdk1 negatively regulates midzone localization of the mitotic kinesin Mklp2 and the chromosomal passenger complex.. Curr Biol 19(7):607-12 PMID: 19303298
- 3. Nakos K et al.. 2025. A minimum module for positioning the Chromosomal Passenger Complex at the cell center for cytokinesis.. bioRxiv PMID: 40950017
- 4. Ballmer D et al.. 2024. Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-B.. Elife 13 PMID: 38564240
- 5. Xu Z et al.. 2009. INCENP-aurora B interactions modulate kinase activity and chromosome passenger complex localization.. J Cell Biol 187(5):637-53 PMID: 19951914
- 6. Platani M et al.. 2009. The Nup107-160 nucleoporin complex promotes mitotic events via control of the localization state of the chromosome passenger complex.. Mol Biol Cell 20(24):5260-75 PMID: 19864462
- 7. Carmena M et al.. 2015. The Dawn of Aurora Kinase Research: From Fly Genetics to the Clinic.. Front Cell Dev Biol 3:73 PMID: 26636082
- 8. Lens SM et al.. 2006. Uncoupling the central spindle-associated function of the chromosomal passenger complex from its role at centromeres.. Mol Biol Cell 17(4):1897-909 PMID: 16436504
