Proteomics

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Aurora kinase B-dependent phosphorylation regulates caspase-2 activity and function


ABSTRACT: Mitotic catastrophe (MC) is an important mechanism to remove cells that become polyploid or aneuploid, as an oncosuppressive mechanism. Previous studies have demonstrated that the activation and catalytic function of caspase-2 is a key step in MC, to trigger apoptosis and/or cell cycle arrest of such defective cells. However, the molecular mechanisms that regulate caspase-2 activation and its function are unclear. Here we show that Aurora kinase B (AURKB), a key mitotic kinase, phosphorylates caspase-2 at a highly conserved residue S384 and inhibits its catalytic activity and function. We identified six new phosphorylation sites in caspase-2 and further demonstrated 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Fibroblast

SUBMITTER: Jarrod Sandow  

LAB HEAD: Sharad Kumar

PROVIDER: PXD017866 | Pride | 2021-09-09

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
P3126_C2PLK1i_1_1_1.raw Raw
P3126_C2PLK1i_1_1_2.raw Raw
P3126_C2_1_1_1.raw Raw
P3126_C2_1_1_2.raw Raw
P3166_C2PLK1i_1_1_3.raw Raw
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Publications

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

Lim Yoon Y   De Bellis Dylan D   Sandow Jarrod J JJ   Capalbo Luisa L   D'Avino Pier Paolo PP   Murphy James M JM   Webb Andrew I AI   Dorstyn Loretta L   Kumar Sharad S  

Cell death and differentiation 20200818 1


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 cas  ...[more]

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