Phosphorylation by Aurora B kinase regulates caspase-2 activity and function
- Author(s)
- Lim, Y; De Bellis, D; Sandow, JJ; Capalbo, L; D'Avino, PP; Murphy, JM; Webb, AI; Dorstyn, L; Kumar, S;
- Journal Title
- Cell Death and Differentiation
- Publication Type
- Journal epub ahead of print
- 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.
- Publisher
- NPG
- Research Division(s)
- Inflammation; Advanced Technology And Biology
- PubMed ID
- 32811973
- Publisher's Version
- https://doi.org/10.1038/s41418-020-00604-y
- Open Access at Publisher's Site
https://doi.org/10.1038/s41418-020-00604-y- NHMRC Grants
- NHMRC/1043057, NHMRC/1103006, NHMRC/1105754, NHMRC/1172929,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-10-02 09:53:37
Last Modified: 2020-10-02 10:11:18