Related Experiment Video
Updated: Dec 7, 2025
06:29
Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
3.3K
SET/TAF1 forms a distance-dependent feedback loop with Aurora B and Bub1 as a tension sensor at centromeres
Yuichiro Asai1, Rieko Matsumura1, Yurina Hasumi1
1Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo, 169-8555, Japan.
Scientific Reports
|September 25, 2020
Summary
A novel feedback loop involving SET, Aurora B kinase, and Bub1 acts as a tension sensor at centromeres, ensuring accurate chromosome segregation during cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Accurate chromosome segregation during mitosis relies on precise spatiotemporal regulation of kinetochore phosphorylation.
- Aurora B kinase corrects improper kinetochore-microtubule attachments, while centromeric tension stabilizes them via PP2A phosphatase.
- The molecular mechanism of tension sensing at centromeres remains unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying tension sensing at centromeres during mitosis.
- To investigate the roles of SET, Aurora B kinase, and Bub1 in regulating kinetochore-microtubule attachment stability.
Main Methods:
- Investigated the interplay between Aurora B kinase, Bub1, and SET localization at centromeres.
- Analyzed the dependence of SET localization on Bub1 kinase activity and its regulation by inter-kinetochore distance.
- Utilized ectopic SET targeting to assess its impact on Aurora B activity and the feedback loop.
Main Results:
- Demonstrated a distance-dependent positive feedback loop between Aurora B and Bub1 at the centromere/kinetochore.
- Showed that centromeric SET localization on Sgo2 is dependent on Bub1 kinase activity and decreases with increasing inter-kinetochore distance.
- Confirmed that ectopic SET targeting hyperactivates Aurora B via PP2A inhibition, rescuing the feedback loop.
Conclusions:
- Proposed that SET, Aurora B, and Bub1 form a distance-dependent positive feedback loop that functions as a spatiotemporal tension sensor at centromeres.
- This regulatory network is crucial for accurate chromosome alignment and segregation during cell division.
Related Concept Videos
02:57Attachment of Sister Chromatids
3.7K
As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules. Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall...
3.7K
01:26Tension Response at Adherens Junctions
3.3K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
3.3K
02:30Histone Variants at the Centromere
4.8K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.8K
01:24Microtubules in Cell Motility
4.3K
Microtubules are thick hollow cylindrical proteins that help form the cytoskeleton. Microtubules have varied roles in the cell. These filaments help form cellular appendages like cilia and flagella, which are responsible for locomotion. The cilia arise from basal bodies, separated from the main body by a membrane-like structure forming the transition zone. This zone is the gate for the entry of lipids and proteins, creating a unique composition of lipids and proteins in the ciliary membrane and...
4.3K
01:39Anaphase A and B
5.1K
Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
5.1K
02:17Microtubule Instability
5.7K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.7K