PXD017866

PXD017866 is an original dataset announced via ProteomeXchange.

Title	Aurora kinase B-dependent phosphorylation regulates caspase-2 activity and function
Description	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.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-08_18:34:29.909.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jarrod Sandow
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-04 02:05:06	ID requested
⏵ 1	2021-09-08 18:34:30	announced

Lim Y, De Bellis D, Sandow JJ, Capalbo L, D'Avino PP, Murphy JM, Webb AI, Dorstyn L, Kumar S, Phosphorylation by Aurora B kinase regulates caspase-2 activity and function. Cell Death Differ, 28(1):349-366(2021) [pubmed]

submitter keyword: Caspase 2, Aurorka kinase, phosphorylation

Sharad Kumar
contact affiliation	The Centre for Cancer Biology
contact email	sharad.kumar@unisa.edu.au
lab head
Jarrod Sandow
contact affiliation	WEHI
contact email	sandow@wehi.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017866
     1. Label: PRIDE project
     2. Name: Aurora kinase B-dependent phosphorylation regulates caspase-2 activity and function