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dc.contributor.authorLim, Yoon
dc.contributor.authorDe Bellis, Dylan
dc.contributor.authorSandow, Jarrod J.
dc.contributor.authorCapalbo, Luisa
dc.contributor.authorD’Avino, Pier Paolo
dc.contributor.authorMurphy, James M.
dc.contributor.authorWebb, Andrew I.
dc.contributor.authorDorstyn, Loretta
dc.contributor.authorKumar, Sharad
dc.date.accessioned2021-01-07T16:22:55Z
dc.date.available2021-01-07T16:22:55Z
dc.date.issued2020-08-18
dc.date.submitted2020-03-19
dc.identifier.issn1350-9047
dc.identifier.others41418-020-00604-y
dc.identifier.other604
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/315827
dc.description.abstractAbstract: 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.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/45/607/468
dc.subject/631/80/474
dc.subject/13
dc.subject/13/2
dc.subject/82/83
dc.subject/96
dc.subject/96/95
dc.subjectarticle
dc.titlePhosphorylation by Aurora B kinase regulates caspase-2 activity and function
dc.typeArticle
dc.date.updated2021-01-07T16:22:53Z
prism.endingPage366
prism.issueIdentifier1
prism.publicationNameCell Death & Differentiation
prism.startingPage349
prism.volume28
dc.identifier.doi10.17863/CAM.62938
dcterms.dateAccepted2020-08-05
rioxxterms.versionofrecord10.1038/s41418-020-00604-y
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidLim, Yoon [0000-0003-1110-1969]
dc.contributor.orcidDe Bellis, Dylan [0000-0002-2741-7004]
dc.contributor.orcidSandow, Jarrod J. [0000-0001-5684-8236]
dc.contributor.orcidD’Avino, Pier Paolo [0000-0002-4773-6950]
dc.contributor.orcidMurphy, James M. [0000-0003-0195-3949]
dc.contributor.orcidWebb, Andrew I. [0000-0001-5061-6995]
dc.contributor.orcidKumar, Sharad [0000-0001-7126-9814]
dc.identifier.eissn1476-5403
pubs.funder-project-idDepartment of Health | National Health and Medical Research Council (NHMRC) (1043057)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)