GO:1903438 positive regulation of mitotic cytokinetic process: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1903438 describes any process that activates or increases the frequency, rate or extent of mitotic cytokinetic process, the final step of cell division.
• Positive regulation ensures faithful chromosome segregation and timely abscission, preventing aneuploidy and genomic instability.
• Key regulators include chromosomal passenger proteins such as Aurora B, INCENP, Survivin, and Borealin, which coordinate cleavage furrow ingression and abscission.
• mTOR autophosphorylation at Ser2481 colocalizes with chromosomal passenger proteins during cytokinesis, linking growth signaling to mitotic exit.
• Dysregulation of cytokinetic positive regulators is implicated in cancer, developmental disorders, and chemotherapy resistance.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable precise dissection of positive regulators in cytokinesis.
Description
Mitotic cytokinesis is the final stage of cell division, physically separating the cytoplasm of two daughter cells. The Gene Ontology term GO:1903438, positive regulation of mitotic cytokinetic process, encompasses any molecular event that enhances the initiation, progression, or completion of this process. Because cytokinesis must be tightly regulated to prevent aneuploidy and tumorigenesis, understanding its positive regulators is critical for basic cell biology and translational research. This article synthesizes authoritative QuickGO annotations and verified PubMed literature to provide a research-grade overview of GO:1903438, covering its definition, molecular players, disease relevance, and CRISPR-based experimental strategies.
positive regulation of mitotic cytokinetic process At A Glance
| GO ID | GO:1903438 |
|---|---|
| GO term | positive regulation of mitotic cytokinetic process |
| Ontology | biological_process |
| Synonym | activation of mitotic cytokinetic process; up regulation of mitotic cytokinetic process; up-regulation of mitotic cytokinetic process; upregulation of mitotic cytokinetic process |
| Major function | Enhances the rate, frequency, or extent of mitotic cytokinesis, ensuring faithful cell division. |
| Related processes | Mitotic cell cycle, cytokinesis, chromosomal passenger complex assembly, abscission. |
| Key regulators | Aurora B kinase, INCENP, Survivin, Borealin, mTOR. |
| Disease relevance | Cancer, developmental disorders, genomic instability. |
What Is GO:1903438?
GO:1903438 is a biological process term defined as any process that activates or increases the frequency, rate or extent of mitotic cytokinetic process. In other words, it includes all molecular functions and pathways that positively drive the physical separation of daughter cells during mitosis, from cleavage furrow ingression to midbody abscission.
Why Is positive regulation of mitotic cytokinetic process Important in Cell Biology?
Positive regulation of mitotic cytokinesis is essential for maintaining genomic stability. Failure to properly execute or regulate cytokinesis leads to binucleation, aneuploidy, and cell death, which are hallmarks of cancer and developmental syndromes. Studying GO:1903438 provides mechanistic insights into how cells ensure accurate division and offers potential therapeutic targets for diseases characterized by aberrant proliferation.
• Prevents aneuploidy by ensuring complete chromosome segregation during mitosis.
• Coordinates cleavage furrow ingression with chromosomal passenger complex activity.
• Links growth signaling pathways, such as mTOR, to mitotic exit.
• Dysregulation is associated with tumorigenesis and cancer progression.
• Mutations in cytokinetic regulators cause developmental disorders and microcephaly.
• Provides targets for anti-cancer therapies that induce cytokinesis failure.
• Essential for stem cell self-renewal and tissue homeostasis.
• Influences chemotherapy sensitivity through mitotic checkpoint control.
What Happens During positive regulation of mitotic cytokinetic process?
Initiation of Cleavage Furrow Ingression
In simple terms: The cell starts to pinch inward to divide into two.
Positive regulation begins with the activation of the chromosomal passenger complex (CPC), comprising Aurora B kinase, INCENP, Survivin, and Borealin. Aurora B phosphorylates substrates at the equatorial cortex, promoting actomyosin ring assembly and cleavage furrow ingression. mTOR autophosphorylation at Ser2481 colocalizes with CPC components, suggesting growth signaling contributes to this initiation.
Elongation and Stabilization of the Intercellular Bridge
In simple terms: The connection between the two new cells is stretched and stabilized.
As ingression proceeds, the intercellular bridge forms and must be stabilized. Positive regulators such as Aurora B maintain phosphorylation of midbody proteins, preventing premature abscission. This step ensures that chromosome segregation is complete before final separation.
Midbody Assembly and Abscission
In simple terms: The final cut that separates the two cells occurs.
The midbody, a dense protein structure, recruits ESCRT machinery for abscission. Positive regulation involves Aurora B-dependent recruitment of factors that promote abscission, including components of the ESCRT-III complex. mTOR Ser2481 autophosphorylation persists at the midbody, potentially coordinating abscission with nutrient status.
Coordination with Mitotic Exit
In simple terms: The cell ensures division is finished before starting other processes.
Positive regulators of cytokinesis are tightly coupled to mitotic exit. Aurora B activity must be downregulated for abscission to complete, and this inactivation is a key regulatory step. mTOR signaling may influence this transition, linking cell growth to division completion.
Key Genes Involved in GO:1903438 positive regulation of mitotic cytokinetic process
The following genes and proteins are central to the positive regulation of mitotic cytokinetic process, based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| AURKB | Chromosomal passenger complex kinase; phosphorylates substrates for furrow ingression and abscission | Target for cancer therapy; knockout causes cytokinesis failure |
| INCENP | Scaffold for CPC; activates Aurora B | Essential for CPC function; mutations linked to developmental disorders |
| BIRC5 (Survivin) | CPC component; regulates Aurora B activity and abscission | Overexpressed in cancers; knockout leads to polyploidy |
| CDCA8 (Borealin) | CPC component; targets CPC to centromeres and midbody | Required for cytokinesis; knockdown causes binucleation |
| MTOR | Ser2481 autophosphorylation colocalizes with CPC during cytokinesis | Links growth signaling to cytokinesis; inhibitor studies |
| RACGAP1 | Rho GTPase activating protein; regulates actomyosin ring | Mutated in cancers; knockout impairs cytokinesis |
| ECT2 | Rho guanine nucleotide exchange factor; activates RhoA for furrow ingression | Overexpressed in tumors; knockout blocks cytokinesis |
| RHOa | Small GTPase; drives actomyosin contractility | Key regulator; dominant-negative mutants inhibit cytokinesis |
| ANLN | Actin-binding protein; required for furrow ingression | Mutated in focal segmental glomerulosclerosis; knockout causes cytokinesis defects |
| KIF23 (MKLP1) | Kinesin motor; central spindle assembly | Essential for midbody formation; knockdown blocks abscission |
| KIF20A | Kinesin motor; transports CPC components | Overexpressed in cancers; knockout impairs cytokinesis |
| PLK1 | Polo-like kinase; regulates CPC and abscission | Inhibitor targets in cancer; knockdown causes cytokinesis failure |
| CEP55 | Midbody protein; recruits ESCRT for abscission | Mutations cause hydranencephaly; knockout blocks abscission |
| CHMP4B | ESCRT-III component; mediates membrane scission | Mutations cause cataracts; knockdown inhibits abscission |
| VPS4 | AAA-ATPase; recycles ESCRT components | Required for abscission; dominant-negative blocks cytokinesis |
| ALIX | ESCRT accessory protein; recruits CHMP4B | Knockout delays abscission |
| TSG101 | ESCRT-I component; involved in midbody abscission | Knockdown causes abscission defects |
| SPASTIN | Microtubule severing enzyme; required for abscission | Mutations cause spastic paraplegia; knockdown blocks abscission |
How Is positive regulation of mitotic cytokinetic process Regulated?
Positive regulation of mitotic cytokinesis is controlled by phosphorylation cascades, primarily driven by Aurora B kinase and Polo-like kinase 1 (PLK1). Aurora B activity is modulated by CPC assembly and localization, which is regulated by INCENP, Survivin, and Borealin. mTOR signaling, through Ser2481 autophosphorylation, colocalizes with CPC components and may integrate nutrient status with cytokinetic progression. Additionally, RhoA GTPase cycling, controlled by ECT2 and RACGAP1, provides spatial regulation of actomyosin contractility. These regulatory layers ensure cytokinesis occurs only after faithful chromosome segregation.
positive regulation of mitotic cytokinetic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| AURKB | Cancer, aneuploidy | Knockout and point mutation cell lines; xenograft models |
| CEP55 | Hydranencephaly | Knock-in of patient mutations in iPSCs; knockout mice |
| CHMP4B | Cataracts | Knockout and knock-in in lens epithelial cells |
| SPASTIN | Hereditary spastic paraplegia | Knockout neurons; overexpression of mutant forms |
| PLK1 | Cancer | Knockout and inhibitor studies in cancer cell lines |
Cancer and Genomic Instability
Dysregulation of positive regulators of cytokinesis, such as AURKB, PLK1, and ECT2, leads to aneuploidy and tumorigenesis. Overexpression of Aurora B and Survivin is observed in multiple cancers and correlates with poor prognosis. Targeting these regulators with small molecule inhibitors is an active therapeutic strategy.
Developmental Disorders
Mutations in cytokinesis genes cause developmental syndromes. For example, mutations in CEP55 result in hydranencephaly, and CHMP4B mutations cause cataracts. These disorders highlight the importance of precise cytokinetic regulation in tissue development.
Neurodegeneration
SPASTIN mutations, which impair abscission, cause hereditary spastic paraplegia. This demonstrates that positive regulation of cytokinesis is critical for neuronal survival and function.
From positive regulation of mitotic cytokinetic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of AURKB block cytokinesis? | CRISPR knockout in HeLa or HEK293T cells |
| Does mTOR Ser2481 phosphorylation regulate abscission? | Point mutation (S2481A) knock-in cell lines |
| Can patient mutations in CEP55 cause abscission defects? | Knock-in of patient alleles in iPSCs |
| Where does Aurora B localize during cytokinesis? | Tagged knock-in (GFP-AURKB) for live imaging |
| Does overexpression of ECT2 drive aneuploidy? | Overexpression cell lines and xenografts |
| What is the role of PLK1 in abscission? | CRISPR knockout and rescue with wild-type or mutant PLK1 |
How to Study the positive regulation of mitotic cytokinetic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Dynamics of furrow ingression and abscission | Assessing positive regulators in real time |
| CRISPR knockout | Loss-of-function phenotypes | Identifying essential cytokinesis genes |
| Phosphoproteomics | Global phosphorylation changes | Mapping Aurora B substrates |
| Proximity ligation assay | Protein-protein interactions in situ | Detecting mTOR-CPC colocalization |
| Flow cytometry | DNA content (polyploidy) | Quantifying cytokinesis failure |
| Immunofluorescence | Localization of midbody proteins | Visualizing abscission defects |
| Western blot | Protein expression and phosphorylation | Validating knockouts and inhibitors |
| Time-lapse microscopy | Cell division duration and success | Screening for cytokinesis regulators |
Live-Cell Imaging
Live-cell imaging with fluorescently tagged proteins (e.g., GFP-Aurora B, mCherry-tubulin) allows real-time visualization of cleavage furrow ingression and abscission. This method is essential for assessing the kinetics of positive regulation.
RNA Interference and CRISPR Knockout
Knockdown or knockout of candidate positive regulators (e.g., AURKB, ECT2) followed by phenotypic analysis (binucleation, multinucleation) identifies essential cytokinesis genes. CRISPR provides stable, complete loss-of-function models.
Phosphoproteomics
Mass spectrometry-based phosphoproteomics can identify substrates of Aurora B and PLK1 during cytokinesis, revealing downstream effectors of positive regulation.
Proximity Ligation Assays
Proximity ligation assays (PLA) detect close proximity of proteins (e.g., mTOR and CPC components) at the midbody, confirming physical interactions during cytokinesis.
How CRISPR Can Be Used to Study GO:1903438 positive regulation of mitotic cytokinetic process
Knockout
CRISPR knockout of positive regulators such as AURKB, ECT2, or PLK1 results in cytokinesis failure, producing binucleated or multinucleated cells. These models are used to confirm essential roles and to study downstream effects on genomic stability.
Point Mutation
Point mutations (e.g., mTOR S2481A) can be introduced via CRISPR to test specific phosphorylation events. Such models help dissect signaling pathways that positively regulate cytokinesis without completely abolishing protein function.
Knock-in
Knock-in of tagged proteins (e.g., GFP-AURKB) or patient mutations (e.g., CEP55) allows live imaging and disease modeling. This approach preserves endogenous regulation and provides physiological relevance.
Overexpression
CRISPR activation or cDNA overexpression of genes like ECT2 or AURKB can drive hyperactivation of cytokinesis, leading to aneuploidy. These models are useful for studying oncogenic roles of positive regulators.
How EDITGENE Supports positive regulation of mitotic cytokinetic process Research
Researchers studying positive regulation of mitotic cytokinetic process-related genes often need to determine whether a candidate gene is causally involved in cytokinesis, and to dissect the precise molecular mechanisms. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of mitotic cytokinetic process research.
Frequently Asked Questions About positive regulation of mitotic cytokinetic process
What is GO:1903438?
GO:1903438 is the Gene Ontology term for positive regulation of mitotic cytokinetic process, describing any process that activates or increases the frequency, rate or extent of mitotic cytokinesis.
What genes are involved in positive regulation of mitotic cytokinetic process?
Key genes include AURKB, INCENP, BIRC5 (Survivin), CDCA8 (Borealin), MTOR, ECT2, RACGAP1, PLK1, and CEP55, among others.
How does mTOR regulate cytokinesis?
mTOR autophosphorylated at Ser2481 colocalizes with chromosomal passenger proteins during cytokinesis, suggesting a role in coordinating growth signaling with mitotic exit.
What happens if cytokinesis is not properly regulated?
Defective positive regulation leads to binucleation, aneuploidy, and genomic instability, which are associated with cancer and developmental disorders.
What is the role of Aurora B in cytokinesis?
Aurora B kinase, part of the chromosomal passenger complex, phosphorylates substrates to drive cleavage furrow ingression and abscission.
Which diseases are linked to cytokinesis defects?
Cytokinesis defects are linked to cancer, hydranencephaly (CEP55 mutations), cataracts (CHMP4B mutations), and hereditary spastic paraplegia (SPASTIN mutations).
How can I study positive regulation of mitotic cytokinetic process?
Use CRISPR knockout, point mutation knock-in, live-cell imaging, and phosphoproteomics to dissect mechanisms and identify regulators.
What CRISPR models are available for cytokinesis research?
Knockout, point mutation, knock-in (tagged or patient mutations), and overexpression models can be generated for any gene of interest.
What is the chromosomal passenger complex?
The CPC is a protein complex of Aurora B, INCENP, Survivin, and Borealin that regulates chromosome segregation and cytokinesis.
How does EDITGENE support cytokinesis research?
EDITGENE offers custom CRISPR cell model generation, library screening, and bioinformatics services to study positive regulators of cytokinesis.
Conclusion
GO:1903438, positive regulation of mitotic cytokinetic process, is a critical biological process ensuring faithful cell division. Its dysregulation contributes to cancer and developmental disorders, making it a rich area for research. By leveraging CRISPR-based models and advanced imaging, researchers can uncover new regulators and therapeutic targets. EDITGENE provides the tools and expertise to accelerate these discoveries.
References
- 1. Vazquez-Martin A et al.. 2012. Ser2481-autophosphorylated mTOR colocalizes with chromosomal passenger proteins during mammalian cell cytokinesis.. Cell Cycle 11(22):4211-21 PMID: 23095638
