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PXD057400

PXD057400 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSelf-priming of Plk1 binding to BubR1 ensures accurate mitotic progression
Description Plk1 is a key mitotic kinase that localizes to distinct subcellular structures to promote accurate mitotic progression. Plk1 recruitment depends on direct interaction between polo-box domain (PBD) on Plk1 and PBD binding motif (PBD BM) on the interactors. However, recent study showed that PBD BM alone is not enough for stable binding between CENP-U and Plk1 highlighting the complexity of the interaction which warrants further investigation. An important interactor for Plk1 during mitosis is the checkpoint protein BubR1. Plk1 bound to BubR1 via PBD interaction with pT620 phosphorylates BubR1 S676/T680 to promote BubR1-PP2A/B56 interaction. The BubR1-PP2A/B56 complex counteracts the destablizing effect on kinetochore-microtubule attachments by mitotic kinases to promote mitotic progression. Here we show that Plk1 phosphorylates T600/T608 on BubR1 and the double phosphorylation is critical for BubR1-Plk1 interaction. A similar mechanism for Plk1-Bub1 interaction also exists indicating a general principle for Plk1 kinetochore recruitment through self-priming. Mechanistically preventing BubR1 T600/T608 phosphorylation impairs chromosome congression and checkpoint silencing by reducing Plk1 and PP2A/B56 binding to BubR1. Increasing the binding affinity towards Plk1 and PP2A/B56 in BubR1 through protein engineering bypasses the requirement of T600/T608 phosphorylation for mitotic progression. These results reveal a new layer of regulation for accurate mitotic progression.
HostingRepositoryMassIVE
AnnounceDate2024-10-31
AnnouncementXMLSubmission_2024-10-31_08:30:47.333.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterArminja Nadine Kettenbach
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListPhospho
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-10-31 07:48:44ID requested
12024-10-31 08:30:47announced
Publication List
no publication
Keyword List
submitter keyword: Mitosis, BubR1, Plk1, DatasetType:Proteomics
Contact List
Arminja Kettenbach
contact affiliationDartmouth College
contact emailArminja.N.Kettenbach@Dartmouth.edu
lab head
Arminja Nadine Kettenbach
contact affiliationDartmouth
contact emailArminja.N.Kettenbach@Dartmouth.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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