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

Authors :
Luisa Capalbo
Jarrod J. Sandow
Yoon Lim
James M. Murphy
Loretta Dorstyn
Andrew I. Webb
Dylan De Bellis
Sharad Kumar
Pier Paolo D'Avino
Lim, Yoon [0000-0003-1110-1969]
De Bellis, Dylan [0000-0002-2741-7004]
Sandow, Jarrod J. [0000-0001-5684-8236]
D’Avino, Pier Paolo [0000-0002-4773-6950]
Murphy, James M. [0000-0003-0195-3949]
Webb, Andrew I. [0000-0001-5061-6995]
Kumar, Sharad [0000-0001-7126-9814]
Apollo - University of Cambridge Repository
Sandow, Jarrod J [0000-0001-5684-8236]
D'Avino, Pier Paolo [0000-0002-4773-6950]
Murphy, James M [0000-0003-0195-3949]
Webb, Andrew I [0000-0001-5061-6995]
Lim, Yoon
De Bellis, Dylan
Sandow, Jarrod J
Capalbo, Luisa
D'Avino, Pier Paolo
Murphy, James M
Webb, Andrew I
Dorstyn, Loretta
Kumar, Sharad
Source :
Cell Death and Differentiation
Publication Year :
2020
Publisher :
Nature Publishing Group UK, 2020.

Abstract

Mitotic catastrophe (MC) is an important oncosuppressive mechanism that serves to eliminate cells that become polyploid or aneuploidy 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.

Details

Database :
OpenAIRE
Journal :
Cell Death and Differentiation
Accession number :
edsair.doi.dedup.....fa194ad98eaa6d6f201a8e83572f39da