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PXD063178

PXD063178 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleParthenolide disrupts mitosis by inhibiting ZNF207/BUGZ-promoted kinetochore microtubule attachment
DescriptionParthenolide is a natural compound that has shown highly promising anticancer activity. Even though its mode of action has been studied for decades, its antimitotic activity has been largely overlooked, limiting the understanding of its full anticancer potential. In this study, we combined click chemistry with quantitative mass spectrometry and cell biology to elucidate the mechanism of action of parthenolide in mitosis. We show that parthenolide does not act as a microtubule-targeting agent in cells. Instead, it binds to the kinetochore protein ZNF207/BUGZ, preventing the establishment of proper kinetochore-microtubule attachment. Our results show that parthenolide covalently binds to Cys54 of BUGZ via Michael addition to its α-methylene-γ-lactone moiety. Since Cys54 is located within the second zinc finger domain of BUGZ microtubule-targeting region, we propose that parthenolide interferes with the microtubule-binding ability of BUGZ, consequently preventing kinetochore-microtubule attachments required for accurate chromosome congression to the spindle equator.
HostingRepositoryPRIDE
AnnounceDate2025-05-27
AnnouncementXMLSubmission_2025-05-27_05:45:00.781.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLuke Gamon
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue
InstrumenttimsTOF Pro; impact II
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-04-22 01:31:33ID requested
12025-05-27 05:45:01announced
Publication List
10.1038/S44318-025-00469-2;
Keyword List
submitter keyword: Impact,TimsTOF, LCMSMS
Contact List
Michael Davies
contact affiliationDepartment of Biomedical Sciences, University of Copenhagen, Denmark
contact emaildavies@sund.ku.dk
lab head
Luke Gamon
contact affiliationThe University of Copenhagen
contact emaillgamon@sund.ku.dk
dataset submitter
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