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PXD012235

PXD012235 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEfficient checkpoint signaling depends on the integrated activities of Bub1 and the RZZ complex
DescriptionKinetochore localized Mad1 is essential for generating a “wait anaphase” signal during mitosis hereby ensuring accurate chromosome segregation. Inconsistent models for the function and quantitative contribution of the two mammalian Mad1 kinetochore receptors: Bub1 and the Rod-Zwilch-ZW10 (RZZ) complex exist. By combining genome editing and RNAi we achieve penetrant removal of Bub1 and Rod in human cells, which reveals that efficient checkpoint signaling depends on the integrated activities of these proteins. Rod removal reduces the proximity of Bub1 and Mad1 and we can bypass the requirement for Rod by tethering Mad1 to kinetochores or increasing the strength of the Bub1-Mad1 interaction. We find that Bub1 has checkpoint functions independent of Mad1 localization that are supported by low levels of Bub1 suggesting a catalytic function. In conclusion, our results support an integrated model for the Mad1 receptors in which the primary role of RZZ is to localize Mad1 at kinetochores to generate the Mad1-Bub1 complex.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:52:05.382.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFabian Coscia
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-01-07 01:34:58ID requested
12019-02-19 08:03:36announced
22019-05-27 01:41:19announcedUpdated publication reference for PubMed record(s): 30782962.
32024-10-22 04:52:12announced2024-10-22: Updated project metadata.
Publication List
Zhang G, Kruse T, Guasch Bold, ú C, Garvanska DH, Coscia F, Mann M, Barisic M, Nilsson J, Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex. EMBO J, 38(7):(2019) [pubmed]
10.15252/embj.2018100977;
Keyword List
curator keyword: Biological
submitter keyword: Mitosis Proteomics BUB1
Contact List
Jakob Nilsson
contact affiliationNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact emailjakob.nilsson@cpr.ku.dk
lab head
Fabian Coscia
contact affiliationMax Delbrueck Center for Molecular Medicine
contact emailfabian.coscia@cpr.ku.dk
dataset submitter
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Dataset FTP location
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