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Type: Journal article
Title: Phosphorylation by Aurora B kinase regulates caspase-2 activity and function.
Author: Lim, Y.
De Bellis, D.
Sandow, J.J.
Capalbo, L.
D'Avino, P.P.
Murphy, J.M.
Webb, A.I.
Dorstyn, L.
Kumar, S.
Citation: Cell Death and Differentiation, 2021; 28(1):349-366
Publisher: Springer Nature
Issue Date: 2021
ISSN: 1350-9047
Statement of
Yoon Lim, Dylan De Bellis, Jarrod J. Sandow, Luisa Capalbo, Pier Paolo D’Avino, James M. Murphy ... Sharad Kumar ... et al.
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.
Description: Accepted: 5 August 2020
Rights: © The Author(s) 2020. This article is published with open access. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.
DOI: 10.1038/s41418-020-00604-y
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Appears in Collections:Aurora harvest 8
Biochemistry publications

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