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PKCɛ switches Aurora B specificity to exit the abscission checkpoint
Tanya Pike1, Nicola Brownlow1, Svend Kjaer2
1Protein Phosphorylation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Nature Communications
|December 23, 2016
Summary
Protein kinase C epsilon (PKCɛ) controls cell division by phosphorylating Aurora B, a key protein in the abscission checkpoint. This ensures proper cell separation and prevents errors like binucleation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The 'NoCut' or Aurora B abscission checkpoint prevents cell division errors when DNA is present in the cleavage furrow.
- Checkpoint failure results in incomplete cell abscission and binucleate cells, phenotypes also seen with Protein Kinase C epsilon (PKCɛ) loss.
Purpose of the Study:
- To investigate the mechanism by which PKCɛ influences the Aurora B-dependent abscission checkpoint.
- To elucidate the role of PKCɛ in regulating cell division and preventing errors.
Main Methods:
- Investigated the interaction between PKCɛ and Aurora B using biochemical assays.
- Utilized cell models to examine the effects of PKCɛ modulation on Aurora B phosphorylation and substrate specificity.
- Employed genetic manipulation, including depletion of CHMP4C and expression of Aurora B mutants, to assess abscission outcomes.
Main Results:
- PKCɛ directly phosphorylates Aurora B at serine 227 (S227).
- This phosphorylation alters Aurora B's substrate specificity, enhancing the phosphorylation of Borealin and other targets.
- Preventing Borealin phosphorylation or expressing a non-phosphorylatable Aurora B mutant (S227A) caused abscission failure.
- Depleting CHMP4C bypassed the PKCɛ-Aurora B pathway, allowing abscission.
Conclusions:
- PKCɛ acts through Aurora B phosphorylation to regulate the abscission checkpoint exit.
- The PKCɛ-Aurora B signaling pathway is crucial for completing cell division and preventing binucleation.
- Targeting this pathway offers insights into controlling cell division fidelity.
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