PXD058824-1

PXD058824 is an original dataset announced via ProteomeXchange.

Title	An Aurora kinase A-BOD1L1-PP2A B56 Axis promotes chromosome segregation fidelity
Description	Cancer cells are often aneuploid and frequently display elevated rates of chromosome mis-segregation, called chromosomal instability (CIN). CIN is caused by hyperstable kinetochore-microtubule (K-MT) attachments that reduce the correction efficiency of erroneous K-MT attachments. UMK57, a chemical agonist of the protein MCAK improves chromosome segregation fidelity in CIN cancer cells by destabilizing K-MT attachments, but cells rapidly develop resistance. To determine the mechanism, we performed unbiased screens which revealed increased phosphorylation in cells adapted to UMK57 at Aurora kinase A phosphoacceptor sites on BOD1L1. BOD1L1 depletion or Aurora kinase A inhibition eliminated resistance to UMK57. BOD1L1 localizes to spindles/kinetochores during mitosis, interacts with the PP2A phosphatase, and regulates phosphorylation levels of kinetochore proteins, chromosome alignment, mitotic progression and fidelity. Moreover, the BOD1L1 gene is mutated in a subset of human cancers, and BOD1L1 depletion reduces cell growth in combination with clinically relevant doses of taxol or Aurora kinase A inhibitor.
HostingRepository	PRIDE
AnnounceDate	2025-02-18
AnnouncementXML	Submission_2025-02-18_10:28:06.298.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Kucharski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-12 12:06:33	ID requested
⏵ 1	2025-02-18 10:28:06	announced

10.1016/J.CELREP.2025.115317;

submitter keyword: kinase, phosphatase, PP2A, kinetochore, Aurora A, BOD1L1

Duane Compton
contact affiliation	Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth
contact email	Duane.A.Compton@dartmouth.edu
lab head
Thomas Kucharski
contact affiliation	McGill University
contact email	thomas.kucharski@mail.mcgill.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/02/PXD058824

PRIDE project URI

• PRIDE
  1. PXD058824
     1. Label: PRIDE project
     2. Name: An Aurora kinase A-BOD1L1-PP2A B56 Axis promotes chromosome segregation fidelity