Related Experiment Video
Updated: Jun 12, 2025
06:29
Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
3.0K
CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2
James Holder1, Jennifer A Miles2,3, Matthew Batchelor2,3
1Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
The EMBO Journal
|September 26, 2024
Summary
CEP192 binding regulates the cell-cycle kinase Aurora-A localization and activity. This complex is crucial for proper spindle assembly and maintaining genome integrity during mitosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Aurora-A is a key cell-cycle kinase vital for mitosis and spindle dynamics.
- Its functions depend on binding partners like CEP192 and TPX2, which control its activity and location.
Purpose of the Study:
- To investigate the structural and functional roles of the centrosomal Aurora-A:CEP192 complex.
- To understand its place within the broader molecular network governing cell division.
Main Methods:
- Structural analysis of the Aurora-A:CEP192 complex.
- Investigated the impact of CEP192 binding on Aurora-A conformations and activity.
- Utilized deletion mutants to assess the functional consequences of disrupted binding.
Main Results:
- CEP192 directly binds Aurora-A, occupying sites for spindle-associated partners and competing with them.
- CEP192 binding alters Aurora-A conformation, affecting TPX2-mediated activation.
- Deletion of the CEP192 binding interface impairs Aurora-A centrosomal accumulation, reduces its phosphorylation, and leads to mitotic errors.
Conclusions:
- The CEP192:Aurora-A complex is essential for regulating spindle function by providing phosphorylated Aurora-A for TPX2 binding.
- A conserved spatial hierarchy involving CEP192 fine-tunes Aurora-A activity, ensuring genome integrity.
Related Concept Videos
02:02Meiosis II
44.9K
Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
44.9K
02:57Attachment of Sister Chromatids
3.2K
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...
3.2K
00:50Anaphase Promoting Complex
2.8K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.8K
01:39Anaphase A and B
4.0K
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...
4.0K
02:15M-Cdk Drives Transition Into Mitosis
5.5K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K
02:17Separation of Sister Chromatids
3.6K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.6K