PXD003806 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2016-03-17 08:09:22 | ID requested | |
⏵ 1 | 2016-03-31 04:13:14 | announced | |
Publication List
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] |
Keyword List
curator keyword: Biological |
submitter keyword: Kinase, phosphorylation, Mad3, S.pombe, spindle, mitosis |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD003806
- Label: PRIDE project
- Name: Mps1(Mph1) Kinase phosphorylates Mad3 to Inhibit Cdc20Slp1 –APC/C and maintain spindle checkpoint arrests