PXD003806

PXD003806 is an original dataset announced via ProteomeXchange.

Title	Mps1(Mph1) Kinase phosphorylates Mad3 to Inhibit Cdc20Slp1 –APC/C and maintain spindle checkpoint arrests
Description	The spindle checkpoint is a mitotic surveillance system which ensures equal segregation of sister chromatids. It delays anaphase onset by inhibiting the action of the E3 ubiquitin ligase known as the anaphase promoting complex or cyclosome (APC/C). Mads/BubR1 is a key component of the mitotic checkpoint complex (MCC) which binds and inhibits the APC/C early in mitosis. Mps1Mph1 kinase is critical for checkpoint signalling and MCC-APC/C inhibition, yet few substrates have been identified. Here we identify Mad3 as a substrate of fission yeast Mps1Mph1 kinase. We map and mutate phosphorylation sites in Mad3, producing mutants that are targeted to kinetochores and assembled into MCC, yet display reduced APC/C binding and are unable to maintain checkpoint arrests. We chow biochemically that Mad3 phospho-mimics are potent APC/C inhibitors in vitro, demonstrating that Mad3p modification can directly influence Cdc20Slp1-APC/C activity. This genetic dissection of APC/C inhibition demonstrates that Mps1Mph1 kinase-dependant modification of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests.
HostingRepository	PRIDE
AnnounceDate	2016-03-31
AnnouncementXML	Submission_2016-03-31_04:13:10.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD003806
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Heather Barker
SpeciesList	scientific name: Schizosaccharomyces pombe; NCBI TaxID: 4896;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2016-03-17 08:09:22	ID requested
⏵ 1	2016-03-31 04:13:14	announced

Zich J, May K, Paraskevopoulos K, Sen O, Syred HM, van der Sar S, Patel H, Moresco JJ, Sarkeshik A, Yates JR, Rappsilber J, Hardwick KG, Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain Spindle Checkpoint Arrests. PLoS Genet, 12(2):e1005834(2016) [pubmed]

curator keyword: Biological

submitter keyword: Kinase, phosphorylation, Mad3, S.pombe, spindle, mitosis

Kevin Hardwick
contact affiliation	University of Edinburgh
contact email	Kevin.Hardwick@ed.ac.uk
lab head
Heather Barker
contact affiliation	The University of Edinburgh
contact email	heather.barker@ed.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003806
     1. Label: PRIDE project
     2. Name: Mps1(Mph1) Kinase phosphorylates Mad3 to Inhibit Cdc20Slp1 –APC/C and maintain spindle checkpoint arrests