Journal article

Phosphorylation by Aurora B kinase regulates caspase-2 activity and function

Yoon Lim, Dylan De Bellis, Jarrod J Sandow, Luisa Capalbo, Pier Paolo D'Avino, James M Murphy, Andrew I Webb, Loretta Dorstyn, Sharad Kumar

Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2020

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 catalyti..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by NHMRC Senior Principal Research Fellowship


Awarded by BBSRC


Awarded by NHMRC


Awarded by NHMRC IRIISS


Funding Acknowledgements

We thank J. Puccini for helping generate the U2OS-CASP2<SUP>-/-</SUP> cell line, A. Villunger for A549 and A549-CASP2<SUP>-/-</SUP> cell lines, CCB Cytometry for DNA content analysis, and members of our laboratory for discussions and useful comments. This project was supported by the National Health and Medical Research Council (NHMRC) of Australia project grants 1043057 and 1156601, an NHMRC Senior Principal Research Fellowship (1103006) and a University of South Australia support package to SK. We acknowledge the support of the Australian Cancer Research Foundation funded Cancer Genomics and Imaging Core Facilities at CCB. JMM acknowledges the NHMRC fellowship (1105754, 1172929) support; JJS, AIW and JMM acknowledge NHMRC IRIISS (9000587); and the work in PPD laboratory is supported by a BBSRC grant (BB/R001227/1).