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dc.contributor.authorLim, Y
dc.contributor.authorDe Bellis, D
dc.contributor.authorSandow, JJ
dc.contributor.authorCapalbo, L
dc.contributor.authorD'Avino, PP
dc.contributor.authorMurphy, JM
dc.contributor.authorWebb, AI
dc.contributor.authorDorstyn, L
dc.contributor.authorKumar, S
dc.date.accessioned2020-11-26T23:14:43Z
dc.date.available2020-11-26T23:14:43Z
dc.date.issued2020-08-18
dc.identifierpii: 10.1038/s41418-020-00604-y
dc.identifier.citationLim, Y., De Bellis, D., Sandow, J. J., Capalbo, L., D'Avino, P. P., Murphy, J. M., Webb, A. I., Dorstyn, L. & Kumar, S. (2020). Phosphorylation by Aurora B kinase regulates caspase-2 activity and function. CELL DEATH AND DIFFERENTIATION, 28 (1), pp.349-366. https://doi.org/10.1038/s41418-020-00604-y.
dc.identifier.issn1350-9047
dc.identifier.urihttp://hdl.handle.net/11343/252162
dc.description.abstractMitotic 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.
dc.languageEnglish
dc.publisherSPRINGERNATURE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titlePhosphorylation by Aurora B kinase regulates caspase-2 activity and function
dc.typeJournal Article
dc.identifier.doi10.1038/s41418-020-00604-y
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleCell Death and Differentiation
melbourne.source.volume28
melbourne.source.issue1
melbourne.source.pages349-366
dc.rights.licenseCC BY
melbourne.elementsid1462913
melbourne.contributor.authorWebb, Andrew
melbourne.contributor.authorMurphy, James
melbourne.contributor.authorSandow, Jarrod
dc.identifier.eissn1476-5403
melbourne.accessrightsOpen Access


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