PXD063178-1

PXD063178 is an original dataset announced via ProteomeXchange.

Title	Parthenolide disrupts mitosis by inhibiting ZNF207/BUGZ-promoted kinetochore microtubule attachment
Description	Parthenolide 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-27
AnnouncementXML	Submission_2025-05-27_05:45:00.781.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luke Gamon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	timsTOF Pro; impact II

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-22 01:31:33	ID requested
⏵ 1	2025-05-27 05:45:01	announced

10.1038/S44318-025-00469-2;

submitter keyword: Impact,TimsTOF, LCMSMS

Michael Davies
contact affiliation	Department of Biomedical Sciences, University of Copenhagen, Denmark
contact email	davies@sund.ku.dk
lab head
Luke Gamon
contact affiliation	The University of Copenhagen
contact email	lgamon@sund.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063178
     1. Label: PRIDE project
     2. Name: Parthenolide disrupts mitosis by inhibiting ZNF207/BUGZ-promoted kinetochore microtubule attachment