Related Experiment Video
Updated: Jul 17, 2026
06:29
Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
Functional interaction of Aurora-A and PP2A during mitosis
Virginie Horn1, Jacques Thélu, Alphonse Garcia
1Institut Albert Bonniot, Centre de Recherche Institut National de la Santé et de la Recherche Médicale, Université Joseph Fourier U 823, Equipe DySAD, Université Joseph Fourier Site Santé, BP 170, F38042, Grenoble Cedex 09, France.
Molecular Biology of the Cell
|January 19, 2007
Summary
Protein phosphatase 2A (PP2A) dephosphorylates Aurora-A at serine 51, promoting its degradation. This finding reveals a key mechanism regulating cell cycle progression and mitosis entry in human cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitosis entry is regulated by Cyclin B1/Cdk1, with Aurora-A kinase controlling its activation.
- Aurora-A activity is normally regulated by degradation via the APC-ubiquitin-proteasome pathway.
- Phosphorylation may inhibit Aurora-A degradation, suggesting a role for phosphatases in releasing this blockade.
Purpose of the Study:
- To investigate the role of protein phosphatase 2A (PP2A) in regulating Aurora-A degradation during mitosis.
- To determine if PP2A interacts with Aurora-A and influences its phosphorylation status.
- To elucidate the specific mechanism by which PP2A controls Aurora-A activity.
Main Methods:
- Immunofluorescence microscopy to assess colocalization of PP2A and Aurora-A.
- Co-immunoprecipitation to confirm interaction between PP2A and Aurora-A.
- Inhibition of PP2A using okadaic acid and RNA interference (RNAi) to study functional consequences.
- Site-directed mutagenesis (S51D) and phosphomimetic peptide assays to analyze the role of Aurora-A serine 51.
Main Results:
- PP2A and Aurora-A colocalize at cell poles during mitosis in human cells.
- PP2A and Aurora-A interact within the same protein complex.
- PP2A inhibition or depletion affects Aurora-A regulation, confirming a functional interaction.
- PP2A/Aurora-A interaction is modulated by Aurora-A S51 phosphorylation status, with S51D mutation promoting and a phosphomimetic peptide inhibiting interaction.
Conclusions:
- PP2A directly interacts with Aurora-A during mitosis.
- PP2A dephosphorylates Aurora-A at serine 51, thereby controlling its degradation.
- This dephosphorylation by PP2A is a critical step in regulating Aurora-A activity and facilitating cell cycle progression through mitosis.
Related Concept Videos
02:57Attachment of Sister Chromatids
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 of a...
02:57Attachment of Sister Chromatids
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 of a...
01:39Anaphase A and B
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...
01:39Anaphase A and B
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...
02:02Meiosis II
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,...
01:57Meiosis II
Meiosis II is the second and final stage of meiosis. It relies on the haploid cells produced during meiosis I, each of which contain only 23 chromosomes—one from each homologous initial pair. Importantly, each chromosome in these cells is composed of two joined copies, and when these cells enter meiosis II, the goal is to separate such sister chromatids using the same microtubule-based network employed in other division processes. The result of meiosis II is two haploid cells, each containing...