Proteomics

Dataset Information

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Mps1(Mph1) Kinase phosphorylates Mad3 to Inhibit Cdc20Slp1 –APC/C and maintain spindle checkpoint arrests


ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Schizosaccharomyces Pombe

TISSUE(S): Cell Suspension Culture, Vegetative Cell (sensu Fungi)

SUBMITTER: Heather Barker  

LAB HEAD: Kevin Hardwick

PROVIDER: PXD003806 | Pride | 2016-03-31

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
E080926_12.RAW Raw
E080926_12.mgf Mgf
E080926_15.RAW Raw
E080926_15.mgf Mgf
F002549.dat-pride.pride.mgf.gz Mgf
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Publications

Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain Spindle Checkpoint Arrests.

Zich Judith J   May Karen K   Paraskevopoulos Konstantinos K   Sen Onur O   Syred Heather M HM   van der Sar Sjaak S   Patel Hitesh H   Moresco James J JJ   Sarkeshik Ali A   Yates John R JR   Rappsilber Juri J   Hardwick Kevin G KG  

PLoS genetics 20160216 2


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). Mad3/BubR1 is a key component of the mitotic checkpoint complex (MCC) which binds and inhibits the APC/C early in mitosis. Mps1(Mph1) kinase is critical for checkpoint signalling and MCC-APC/C inhibition, yet few substrates have been identified. Here  ...[more]

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