PXD046458

PXD046458 is an original dataset announced via ProteomeXchange.

Title	Spatial control of the APC/C ensures the rapid degradation of Cyclin B1
Description	The proper control of mitosis depends on the ubiquitin-mediated degradation of the right mitotic regulator at the right time. This is under the control of the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase that is regulated by the Spindle Assembly Checkpoint (SAC). The Checkpoint prevents the APC/C from recognizing Cyclin B1, the essential anaphase and cytokinesis inhibitor, until all chromosomes are attached to the spindle. Once chromosomes are attached, Cyclin B1 is rapidly degraded to enable chromosome segregation and cytokinesis. We have a good understanding of how the SAC inhibits the APC/C, but relatively little is known about how the APC/C recognises Cyclin B1 as soon as the SAC is turned off. Here, by combining live cell imaging, in vitro reconstitution, biochemistry, and structural analysis by cryo-electron microscopy, we provide evidence that the rapid recognition of Cyclin B1 in metaphase requires spatial regulation of the APC/C. Using fluorescence cross correlation spectroscopy, we find that Cyclin B1 and the APC/C primarily interact at the mitotic apparatus. We further show that this is because Cyclin B1, like the APC/C, binds to nucleosomes, and identify an ‘arginine-anchor’ in the N-terminus as necessary and sufficient for binding to the nucleosome. Mutating the nucleosome binding motif on Cyclin B1 reduces its interaction with APC/C and delays its degradation, and cells with the mutant, non-nucleosome-binding Cyclin B1 become aneuploid, demonstrating the physiological relevance of our findings. Together, our data demonstrate that mitotic chromosomes constitute a platform to promote the efficient interaction between Cyclin B1 and APC/C and ensure the timely degradation of Cyclin B1 and genomic stability.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_11:56:43.360.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-27 07:39:44	ID requested
⏵ 1	2025-05-06 11:56:44	announced

Cirillo L, Young R, Veerapathiran S, Roberti A, Martin M, Abubacar A, Perosa C, Coates C, Muhammad R, Roumeliotis TI, Choudhary JS, Alfieri C, Pines J, Spatial control of the APC/C ensures the rapid degradation of cyclin B1. EMBO J, 43(19):4324-4355(2024) [pubmed]

10.1038/s44318-024-00194-2;

submitter keyword: ubiquitin-mediated degradation, mitosis, spindle assembly checkpoint,human

Jyoti Choudhary
contact affiliation	Functional Proteomics, ICR
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
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/2025/05/PXD046458

PRIDE project URI

• PRIDE
  1. PXD046458
     1. Label: PRIDE project
     2. Name: Spatial control of the APC/C ensures the rapid degradation of Cyclin B1