PXD056173-1

PXD056173 is an original dataset announced via ProteomeXchange.

Title	Proximity-based activation of AURORA A by MPS1 potentiates error correction
Description	Faithfull cell division relies on mitotic chromosomes becoming bioriented with each pair of sister kinetochores bound to microtubules from opposing spindle poles. Erroneous kinetochore- microtubule attachments often form during early mitosis, but are destabilized through the phosphorylation of outer kinetochore proteins by centromeric AURORA B kinase (ABK) and centrosomal AURORA A kinase (AAK), thus allowing for re-establishment of attachments until biorientation is achieved. MPS1-mediated phosphorylation of NDC80 has also been shown to directly weaken the kinetochore-microtubule interface in yeast. In human cells, MPS1 has been proposed to transiently accumulate at end-on attached kinetochores and phosphorylate SKA3 to promote microtubule release. Whether MPS1 directly targets NDC80 and/or promotes the activity of AURORA kinases in metazoans remains unclear. Here, we report a novel mechanism involving communication between kinetochores and centrosomes, wherein MPS1 acts upstream of AAK to promote error correction. MPS1 on pole-proximal kinetochores phosphorylates the C-lobe of AAK thereby increasing its activation at centrosomes. This proximity-based activation ensures the establishment of a robust AAK activity gradient that locally destabilizes mal-oriented kinetochores near spindle poles. Accordingly, MPS1 depletion from Drosophila cells causes severe chromosome misalignment and erroneous kinetochore-microtubule attachments, which can be rescued by tethering either MPS1 or constitutively active AAK mutants to centrosomes. Proximity-based activation of AAK by MPS1 also occurs in human cells to promote AAK-mediated phosphorylation of the NDC80 N-terminal tail. These findings uncover an MPS1-AAK cross-talk that is required for efficient error correction, showcasing the ability of kinetochores to modulate centrosome outputs to ensure proper chromosome segregation.
HostingRepository	PRIDE
AnnounceDate	2025-04-03
AnnouncementXML	Submission_2025-04-03_08:45:33.896.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tanja Bange
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-24 06:24:45	ID requested
⏵ 1	2025-04-03 08:45:34	announced

Dataset with its publication pending

submitter keyword: auroraA, in vitro phosphorylation assay,mitosis

Tanja Bange
contact affiliation	Institute of Medical Psychology and Biomedical Center (BMC), Faculty of Medicine, LMU 80336 Munich, Germany
contact email	Tanja.Bange@med.uni-muenchen.de
lab head
Tanja Bange
contact affiliation	LMU Munich
contact email	tanja.bange@med.uni-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056173
     1. Label: PRIDE project
     2. Name: Proximity-based activation of AURORA A by MPS1 potentiates error correction