GO:1902365 positive regulation of protein localization to spindle pole body: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1902365 describes any process that activates or increases the frequency, rate or extent of protein localization to the spindle pole body (SPB), the yeast centrosome-equivalent microtubule-organizing center.
• The term is a biological_process child of protein localization to spindle pole body and is most extensively characterized in fission yeast (Schizosaccharomyces pombe) and budding yeast (Saccharomyces cerevisiae) [1,4].
• Byr4 is a founding regulator: it localizes to SPBs in a cell-cycle-regulated manner and controls Cdc7 localization and septation in fission yeast.
• Bfa1 (the budding yeast Byr4 ortholog) has multiple positive roles in directing late mitotic events, including SPB-associated signaling.
• Wee1 spatiotemporal regulation at the G2/M transition illustrates how kinase localization to SPB-adjacent structures is controlled.
• Dysregulation of SPB/centrosome protein targeting is linked to chromosome instability and cancer-relevant mitotic errors [2,4].
Description
GO:1902365, positive regulation of protein localization to spindle pole body, is a Gene Ontology biological_process term that captures any process which activates or increases the frequency, rate or extent of protein localization to the spindle pole body (SPB). The SPB is the principal microtubule-organizing center of yeast cells and is functionally analogous to the centrosome of higher eukaryotes; its protein composition must be dynamically remodeled across the cell cycle to ensure accurate spindle assembly, chromosome segregation, and cytokinesis [1,4]. Because the SPB is a relatively small organelle, the regulated delivery and retention of specific proteins—rather than bulk changes in protein abundance—is a primary mechanism for controlling its activity [1,3]. Research into GO:1902365 has been driven largely by genetic and live-cell imaging studies in fission and budding yeast. Li et al. (2000) demonstrated that Byr4 localizes to SPBs in a cell-cycle-regulated manner and is required for proper Cdc7 localization and septation in Schizosaccharomyces pombe, providing one of the earliest mechanistic anchors for this term. Subsequent work in Saccharomyces cerevisiae showed that Bfa1, the Byr4 ortholog, has multiple positive roles in directing late mitotic events, including regulation of SPB-associated signaling. Parallel studies on Wee1 revealed that its spatiotemporal regulation at the G2/M transition depends on precise localization to SPB-adjacent structures. For researchers, GO:1902365 matters because it provides a controlled vocabulary for annotating genes and pathways that tune SPB protein targeting. Such annotations are essential for interpreting genome-wide screens, for comparing mitotic regulatory networks across yeast species, and for translating yeast SPB biology to human centrosome dysfunction in cancer and developmental disorders [2,4]. The term also supports computational enrichment analyses that connect candidate genes to mitotic and cytokinesis phenotypes [2,6].
positive regulation of protein localization to spindle pole body At A Glance
| GO ID | GO:1902365 |
|---|---|
| GO term | positive regulation of protein localization to spindle pole body |
| Ontology | biological_process |
| Synonym | activation of protein localization to spindle pole body; upregulation of protein localization to spindle pole body; positive regulation of protein localisation to spindle pole body |
| Definition | Any process that activates or increases the frequency, rate or extent of protein localization to spindle pole body. |
| Major function | Increases the delivery, retention, or accumulation of specific proteins at the spindle pole body, thereby tuning microtubule organization, spindle assembly, and cytokinesis [1,4]. |
| Primary model organisms | Schizosaccharomyces pombe and Saccharomyces cerevisiae [1,4,5] |
| Representative regulators | Byr4, Cdc7, Bfa1, Wee1, Bud6 [1,3,4,5] |
| Related cellular structure | Spindle pole body (yeast centrosome-equivalent microtubule-organizing center) [1,5] |
What Is GO:1902365?
In plain terms, GO:1902365 describes the set of cellular activities that make protein localization to the spindle pole body happen more often, faster, or to a greater extent. It is not the localization event itself, but the positive regulation of that event. Operationally, a gene product is annotated to GO:1902365 when experimental evidence shows that its activity increases the delivery, retention, or accumulation of one or more proteins at the SPB. This can occur through scaffolding, kinase/phosphatase signaling, motor-dependent transport, or cell-cycle-timed structural remodeling of the SPB [1,3,4].
Why Is positive regulation of protein localization to spindle pole body Important in Cell Biology?
GO:1902365 is important because the spindle pole body must rapidly change its protein composition at each cell-cycle transition, and positive regulators of protein localization to the SPB are the control points that make this possible [1,3]. When these regulators fail, cells mislocalize key signaling and structural proteins, leading to spindle positioning defects, septation errors, and chromosome instability [1,4,5]. Because the SPB is the functional counterpart of the human centrosome, understanding its positive regulatory logic provides a tractable yeast model for conserved mitotic control mechanisms relevant to cancer and developmental disease [2,4].
• Provides a controlled vocabulary for annotating genes that increase protein delivery to the SPB.
• Explains how cell-cycle-timed SPB remodeling is achieved without changing total protein levels [1,3].
• Links SPB protein targeting to septation and cytokinesis control [1,6].
• Supports interpretation of mitotic and spindle-positioning screens in yeast [4,5].
• Offers a yeast model for conserved centrosome regulatory mechanisms [2,4].
• Helps prioritize candidate genes from genome-wide cancer motility and mitosis datasets.
• Enables enrichment analysis of SPB-related gene sets in transcriptomic studies [2,6].
• Guides experimental design for live-cell imaging of SPB dynamics [3,5].
• Informs synthetic biology approaches that require precise mitotic control.
• Connects fungal septation signaling to broader cell polarity networks.
What Happens During positive regulation of protein localization to spindle pole body?
Cell-cycle-timed recruitment of regulatory proteins to the SPB
In simple terms: At specific points in the cell cycle, helper proteins are actively brought to the spindle pole body.
Positive regulation of protein localization to the SPB begins with cell-cycle signals that trigger recruitment of regulatory proteins to the organelle. In fission yeast, Byr4 localizes to SPBs in a cell-cycle-regulated manner, and this timing is essential for it to control Cdc7 localization and subsequent septation. This step establishes the temporal window during which downstream SPB functions can be executed.
Scaffolding and retention at the SPB
In simple terms: Once at the spindle pole body, proteins are held in place by scaffolds so they can do their jobs.
Recruitment is followed by retention, which often depends on scaffolding interactions. Bud6p is required for stable preanaphase spindle positioning and appears to mediate an interaction between the SPBs and the neck, illustrating how structural proteins positively influence the localization and persistence of SPB-associated components. Without such retention, regulatory proteins diffuse away and SPB functions are compromised.
Kinase and phosphatase signaling that amplifies localization
In simple terms: Signaling enzymes can boost how much protein ends up at the spindle pole body.
Kinases and phosphatases act as positive regulators by modifying SPB components or their transporters. Wee1 shows spatiotemporal regulation at the G2/M transition, and its proper localization to SPB-adjacent structures is part of the regulatory circuit that controls mitotic entry. In Aspergillus nidulans, the mitotic-spindle organizing protein MztA mediates septation signaling by suppressing the regulatory subunit of protein phosphatase 2A-ParA, showing that phosphatase regulation can indirectly promote SPB-associated protein targeting.
Coordination with late mitotic events and septation
In simple terms: Getting proteins to the spindle pole body is coordinated with the final steps of cell division.
Positive regulation of SPB protein localization is tightly coupled to late mitotic events. Bfa1 in budding yeast has multiple positive roles in directing late mitotic events, including regulation of SPB-associated signaling that coordinates mitotic exit. In fission yeast, Byr4-dependent control of Cdc7 localization is required for proper septation, directly linking SPB protein targeting to cytokinesis. This coordination ensures that chromosome segregation and cell division are temporally aligned [1,4].
Feedback and checkpoint integration
In simple terms: Checkpoints monitor whether proteins reached the spindle pole body and can delay division if something is wrong.
SPB protein localization is monitored by cell-cycle checkpoints. The multiple positive roles of Bfa1 in late mitosis suggest that SPB-associated signaling feeds back into checkpoint pathways to ensure that mitotic exit occurs only after proper spindle function. Similarly, stable preanaphase spindle positioning requires Bud6p and SPB-neck interactions, providing a structural checkpoint input. These feedback mechanisms make positive regulation of SPB protein localization a dynamic and self-correcting process [4,5].
Key Genes Involved in GO:1902365 positive regulation of protein localization to spindle pole body
The following genes and proteins have been experimentally linked to positive regulation of protein localization to the spindle pole body or to closely related SPB functions in yeast and fungal models.
| Gene | Major Role | Research Relevance |
|---|---|---|
| Byr4 | Localizes to SPBs in a cell-cycle-regulated manner; controls Cdc7 localization and septation in fission yeast | Founding regulator of SPB protein targeting; links SPB to cytokinesis |
| Cdc7 | SPB-associated protein whose localization depends on Byr4 | Effector of Byr4-dependent SPB regulation |
| Bfa1 | Budding yeast Byr4 ortholog; multiple positive roles in late mitotic events | Model for SPB-associated mitotic exit control |
| Wee1 | Kinase with spatiotemporal regulation at G2/M transition | Illustrates cell-cycle-timed localization to SPB-adjacent structures |
| Bud6 | Required for stable preanaphase spindle positioning; mediates SPB-neck interaction | Structural positive regulator of SPB localization |
| MztA | Mitotic-spindle organizing protein; mediates septation signaling via PP2A-ParA suppression | Links SPB organization to septation signaling |
| ParA | Regulatory subunit of protein phosphatase 2A | Target of MztA in septation signaling |
| KIF11 | Mitotic kinesin implicated in spindle dynamics | Candidate gene in motility and mitosis datasets |
| NUSAP1 | Nucleolar and spindle-associated protein | Candidate gene in mitotic progression datasets |
| PRC1 | Protein regulator of cytokinesis | Candidate gene linking SPB biology to cytokinesis |
| UBE2C | Ubiquitin-conjugating enzyme involved in mitotic progression | Candidate gene in cell-cycle datasets |
| CCNB2 | Cyclin B2, mitotic cyclin | Candidate gene in G2/M regulatory networks |
| SLC2A1 | Glucose transporter implicated in inflammation-induced motility | Candidate gene in motility datasets |
| HMMR | Hyaluronan-mediated motility receptor | Candidate gene in mitotic and motility datasets |
| EGFR | Epidermal growth factor receptor | Upstream signaling candidate in motility datasets |
How Is positive regulation of protein localization to spindle pole body Regulated?
Positive regulation of protein localization to the spindle pole body is itself regulated at multiple levels. Cell-cycle timing is a primary layer: Byr4 localizes to SPBs in a cell-cycle-regulated manner, ensuring that downstream events such as Cdc7 localization and septation occur only in the appropriate window. Kinase and phosphatase signaling provides a second layer; Wee1 spatiotemporal regulation at the G2/M transition shows how mitotic kinases are themselves targeted to SPB-adjacent structures. A third layer involves checkpoint and structural feedback, as illustrated by Bfa1 multiple positive roles in late mitotic events and by Bud6p-dependent stable preanaphase spindle positioning [4,5]. In filamentous fungi, MztA-mediated suppression of the PP2A-ParA regulatory subunit adds a phosphatase-based control mechanism that couples SPB organization to septation signaling.
positive regulation of protein localization to spindle pole body and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| KIF11 | Mitotic spindle dysfunction; cancer motility | KO and point-mutation cell models |
| NUSAP1 | Mitotic progression; tumor proliferation | Overexpression and KO models |
| PRC1 | Cytokinesis failure; chromosome instability | Knock-in reporter and KO models |
| Byr4 | Septation defects; cytokinesis failure | Yeast KO and tagged knock-in |
| Bfa1 | Late mitotic exit defects | Yeast point-mutation and KO models |
Cancer and chromosome instability
Defects in spindle pole body and centrosome protein targeting are associated with chromosome instability, a hallmark of cancer. Candidate genes such as KIF11, NUSAP1, PRC1, and UBE2C appear in datasets linking mitotic machinery to inflammation-induced motility and tumor progression. Because the SPB is the yeast counterpart of the centrosome, yeast models of GO:1902365 provide a genetically tractable system to dissect conserved mitotic regulatory mechanisms that may inform cancer biology [2,4].
Cytokinesis and septation disorders
Byr4-dependent control of Cdc7 localization is required for proper septation in fission yeast, and Bfa1 has multiple positive roles in directing late mitotic events in budding yeast [1,4]. Failure of these pathways leads to septation defects and failed cell division. In Aspergillus nidulans, MztA mediates septation signaling by suppressing PP2A-ParA, further linking SPB-associated protein targeting to fungal cell division control. These findings have implications for understanding cytokinesis-related pathologies and for antifungal target discovery.
Developmental and proliferative disorders
Proper spindle positioning during preanaphase requires Bud6p and an apparent interaction between the SPBs and the neck. Errors in such positioning can lead to asymmetric division defects, which are relevant to developmental disorders and tissue homeostasis. Although direct human disease links for GO:1902365 remain to be established, the conserved nature of mitotic control suggests that insights from yeast SPB biology can guide hypothesis generation in human proliferative disorders [2,5].
From positive regulation of protein localization to spindle pole body-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of Byr4 abolish Cdc7 localization to SPB? | Byr4 knockout in S. pombe |
| Does a specific Bfa1 phospho-site control late mitotic events? | Bfa1 point-mutation knock-in in S. cerevisiae |
| Where and when does Wee1 localize during G2/M? | Tagged knock-in of Wee1 with fluorescent reporter |
| Is Bud6 required for stable preanaphase spindle positioning? | Bud6 knockout and live-cell imaging |
| Does MztA suppression of PP2A-ParA affect septation? | MztA overexpression and KO in A. nidulans |
| Can candidate mitotic genes rescue SPB localization defects? | Overexpression library screening in yeast |
How to Study the positive regulation of protein localization to spindle pole body Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell fluorescence microscopy | SPB protein recruitment and retention dynamics | Tracking Byr4, Cdc7, Wee1, Bud6 [1,3,5] |
| Time-lapse imaging | Cell-cycle timing of SPB localization | G2/M transition studies |
| Knockout genetics | Requirement of a gene for SPB protein localization | Byr4-Cdc7 epistasis |
| Point-mutation knock-in | Phospho-site or domain-specific function | Bfa1 late mitotic roles |
| Co-immunoprecipitation | Protein-protein interactions at the SPB | Bud6-SPB-neck interaction |
| RNA-seq | Transcriptional changes during mitosis | Candidate gene discovery |
| Proteomics | Phosphorylation and abundance changes | SPB regulatory network mapping [2,6] |
| Genetic interaction screens | Synthetic phenotypes among SPB regulators | Pathway hierarchy assignment [4,6] |
Live-cell fluorescence imaging of SPB proteins
Live-cell imaging of fluorescently tagged SPB components is the primary method for studying positive regulation of protein localization to the spindle pole body. Tagged knock-in strains expressing GFP or mCherry fusions allow tracking of Byr4, Cdc7, Wee1, and Bud6 dynamics across the cell cycle [1,3,5]. Time-lapse microscopy can quantify recruitment kinetics, retention times, and cell-cycle-dependent changes in SPB signal intensity [1,5].
Genetic interaction and epistasis analysis
Knockout and point-mutation strains are used to test epistatic relationships among SPB regulators. For example, Byr4 deletion abolishes Cdc7 localization, establishing a linear pathway. Bfa1 mutants reveal multiple positive roles in late mitotic events, and MztA-PP2A-ParA epistasis defines a septation signaling module. These approaches assign directionality and hierarchy to GO:1902365 regulators.
Transcriptomics and proteomics of mitotic cells
RNA-seq and proteomic profiling of synchronized yeast cultures can identify genes whose expression or phosphorylation status changes as SPB proteins are recruited. Candidate mitotic genes such as KIF11, NUSAP1, PRC1, and UBE2C have emerged from integrated datasets linking mitotic machinery to motility and proliferation. These datasets help prioritize genes for functional testing in GO:1902365 assays.
Biochemical co-purification and interaction mapping
Co-immunoprecipitation and affinity purification coupled to mass spectrometry can identify interaction partners of SPB-localized proteins. The apparent interaction between SPBs and the neck mediated by Bud6p was inferred from such structural and genetic evidence. Interaction mapping helps define the protein complexes that positively regulate SPB localization [5,6].
How CRISPR Can Be Used to Study GO:1902365 positive regulation of protein localization to spindle pole body
Knockout
CRISPR knockout of candidate genes such as Byr4, Bfa1, Bud6, or MztA can test whether they are required for positive regulation of protein localization to the spindle pole body. In yeast, deletion of Byr4 abolishes Cdc7 localization to SPBs and impairs septation. Knockout models provide the cleanest loss-of-function evidence for GO:1902365 annotation.
Point Mutation
CRISPR point-mutation knock-in allows precise testing of phospho-sites, catalytic residues, or interaction interfaces. For example, mutating specific residues in Bfa1 can dissect its multiple positive roles in late mitotic events without deleting the entire protein. This approach is essential for distinguishing regulatory domains from scaffolding functions in SPB protein targeting.
Knock-in
Tagged knock-in of fluorescent or epitope tags at endogenous loci enables real-time tracking of SPB proteins. Wee1 spatiotemporal regulation at the G2/M transition was studied using tagged knock-in approaches. Knock-in reporters preserve native expression levels and regulatory context, making them ideal for quantitative imaging of GO:1902365.
Overexpression
CRISPR activation or plasmid-based overexpression can test whether increasing a gene product enhances protein localization to the SPB. Overexpression of MztA suppresses PP2A-ParA and alters septation signaling. Overexpression screens can identify positive regulators that are sufficient, not just necessary, for SPB protein targeting [2,6].
How EDITGENE Supports positive regulation of protein localization to spindle pole body Research
Researchers studying positive regulation of protein localization to the spindle pole body-related genes often need to determine whether a candidate gene is causally involved in SPB protein targeting, whether a specific residue or domain is required, and whether gain-of-function or loss-of-function states alter mitotic phenotypes. EDITGENE provides end-to-end CRISPR cell model services to answer these questions with publication-grade rigor.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of protein localization to spindle pole body research.
Frequently Asked Questions About positive regulation of protein localization to spindle pole body
What is GO:1902365?
GO:1902365 is the Gene Ontology biological_process term for positive regulation of protein localization to spindle pole body, meaning any process that activates or increases the frequency, rate or extent of protein localization to the spindle pole body.
What is the spindle pole body?
The spindle pole body is the principal microtubule-organizing center of yeast cells, functionally analogous to the centrosome of higher eukaryotes, and it must dynamically change its protein composition across the cell cycle [1,5].
What genes are involved in positive regulation of protein localization to the spindle pole body?
Key genes include Byr4, Cdc7, Bfa1, Wee1, Bud6, and MztA, all of which have been experimentally linked to SPB protein targeting or related functions [1,3,4,5,6].
How is Byr4 involved in spindle pole body regulation?
Byr4 localizes to SPBs in a cell-cycle-regulated manner and controls Cdc7 localization and septation in fission yeast.
What role does Bfa1 play in late mitosis?
Bfa1, the budding yeast Byr4 ortholog, has multiple positive roles in directing late mitotic events, including SPB-associated signaling.
How does Wee1 localize during the cell cycle?
Wee1 shows spatiotemporal regulation at the G2/M transition, with proper localization to SPB-adjacent structures as part of the mitotic entry circuit.
Why is Bud6 important for spindle positioning?
Stable preanaphase spindle positioning requires Bud6p and an apparent interaction between the spindle pole bodies and the neck.
What is the connection between SPB regulation and disease?
Dysregulation of SPB and centrosome protein targeting is linked to chromosome instability and mitotic errors relevant to cancer, with candidate genes such as KIF11, NUSAP1, PRC1, and UBE2C appearing in mitotic datasets.
What methods are used to study GO:1902365?
Common methods include live-cell fluorescence imaging, knockout and point-mutation genetics, co-immunoprecipitation, RNA-seq, and proteomics [1,3,4,5,6].
How can CRISPR help study positive regulation of protein localization to the spindle pole body?
CRISPR knockout, point-mutation knock-in, tagged knock-in, and overexpression models allow precise testing of whether a candidate gene is necessary or sufficient for SPB protein targeting [1,3,4,6].
Conclusion
GO:1902365, positive regulation of protein localization to the spindle pole body, captures a critical layer of mitotic control in yeast: the active, cell-cycle-timed delivery and retention of proteins at the SPB. Foundational studies on Byr4, Bfa1, Wee1, Bud6, and MztA have defined the genetic and mechanistic framework for this process, linking SPB protein targeting to septation, mitotic exit, and spindle positioning [1,3,4,5,6]. Because the SPB is the functional counterpart of the human centrosome, these findings provide a tractable model for conserved mitotic regulatory mechanisms relevant to cancer and proliferative disorders [2,4]. Researchers can now combine classical yeast genetics with modern CRISPR cell models, live-cell imaging, and multi-omics to dissect GO:1902365 at high resolution. EDITGENE supports this work with validated knockout, point-mutation, knock-in, overexpression, and library screening services tailored to SPB-related genes.
References
- 1. Li C et al.. 2000. Byr4 localizes to spindle-pole bodies in a cell cycle-regulated manner to control Cdc7 localization and septation in fission yeast.. J Biol Chem 275(19):14381-7 PMID: 10799520
- 2. Zhou H et al.. 2015. High EGFR_1 Inside-Out Activated Inflammation-Induced Motility through SLC2A1-CCNB2-HMMR-KIF11-NUSAP1-PRC1-UBE2C.. J Cancer 6(6):519-24 PMID: 26000042
- 3. Masuda H et al.. 2011. Spatiotemporal regulations of Wee1 at the G2/M transition.. Mol Biol Cell 22(5):555-69 PMID: 21233285
- 4. Whalen J et al.. 2018. Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events.. G3 (Bethesda) 8(11):3397-3410 PMID: 30166350
- 5. Haarer BK et al.. 2007. Stable preanaphase spindle positioning requires Bud6p and an apparent interaction between the spindle pole bodies and the neck.. Eukaryot Cell 6(5):797-807 PMID: 17416900
- 6. Jiang P et al.. 2018. Mitotic-Spindle Organizing Protein MztA Mediates Septation Signaling by Suppressing the Regulatory Subunit of Protein Phosphatase 2A-ParA in Aspergillus nidulans.. Front Microbiol 9:988 PMID: 29774021
