Phosphorylation by Aurora B kinase regulates caspase-2 activity and function.
Authors
Capalbo, Luisa
Dorstyn, Loretta
Publication Date
2021-01Journal Title
Cell Death Differ
ISSN
1350-9047
Publisher
Springer Science and Business Media LLC
Volume
28
Issue
1
Pages
349-366
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Lim, Y., De Bellis, D., Sandow, J. J., Capalbo, L., D'Avino, P. P., Murphy, J. M., Webb, A. I., et al. (2021). Phosphorylation by Aurora B kinase regulates caspase-2 activity and function.. Cell Death Differ, 28 (1), 349-366. https://doi.org/10.1038/s41418-020-00604-y
Abstract
Mitotic catastrophe (MC) is an important oncosuppressive mechanism that serves to eliminate cells that become polyploid or aneuploid due to aberrant mitosis. Previous studies have demonstrated that the activation and catalytic function of caspase-2 are key steps in MC to trigger apoptosis and/or cell cycle arrest of mitotically defective cells. However, the molecular mechanisms that regulate caspase-2 activation and its function are unclear. Here, we identify six new phosphorylation sites in caspase-2 and show that a key mitotic kinase, Aurora B kinase (AURKB), phosphorylates caspase-2 at the highly conserved residue S384. We demonstrate that phosphorylation at S384 blocks caspase-2 catalytic activity and apoptosis function in response to mitotic insults, without affecting caspase-2 dimerisation. Moreover, molecular modelling suggests that phosphorylation at S384 may affect substrate binding by caspase-2. We propose that caspase-2 S384 phosphorylation by AURKB is a key mechanism that controls caspase-2 activation during mitosis.
Keywords
Article, /631/45/607/468, /631/80/474, /13, /13/2, /82/83, /96, /96/95, article
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/R001227/1)
Identifiers
s41418-020-00604-y, 604
External DOI: https://doi.org/10.1038/s41418-020-00604-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330144
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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