PXD012235

PXD012235 is an original dataset announced via ProteomeXchange.

Title	Efficient checkpoint signaling depends on the integrated activities of Bub1 and the RZZ complex
Description	Kinetochore 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:52:05.382.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabian Coscia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-07 01:34:58	ID requested
1	2019-02-19 08:03:36	announced
2	2019-05-27 01:41:19	announced	Updated publication reference for PubMed record(s): 30782962.
⏵ 3	2024-10-22 04:52:12	announced	2024-10-22: Updated project metadata.

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;

curator keyword: Biological

submitter keyword: Mitosis Proteomics BUB1

Jakob Nilsson
contact affiliation	Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	jakob.nilsson@cpr.ku.dk
lab head
Fabian Coscia
contact affiliation	Max Delbrueck Center for Molecular Medicine
contact email	fabian.coscia@cpr.ku.dk
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/2019/02/PXD012235

PRIDE project URI

• PRIDE
  1. PXD012235
     1. Label: PRIDE project
     2. Name: Efficient checkpoint signaling depends on the integrated activities of Bub1 and the RZZ complex