PXD019788-1

PXD019788 is an original dataset announced via ProteomeXchange.

Title	Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit
Description	APC/C-mediated proteolysis of cyclin B and securin promotes entry into anaphase, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-opposing phosphatases PP1 and PP2A-B55 leading to dephosphorylation of substrates crucial for mitotic exit. Meanwhile, continued APC/C activity is required to target various proteins, including Aurora and Polo kinases, for degradation. Together, these activities orchestrate a complex series of events during mitotic exit. However, the relative importance of regulated proteolysis and dephosphorylation in dictating the order and timing of these events remains unclear. Using high temporal-resolution mass spectrometry, we compare the relative extent of proteolysis and protein dephosphorylation. This reveals highly-selective rapid (~5min half-life) proteolysis of cyclin B, securin and geminin at the metaphase to anaphase transition, followed by slow proteolysis (>60 min half-life) of other mitotic regulators. Protein dephosphorylation requires APC/C-dependent destruction of cyclin B and was resolved into PP1-dependent fast, intermediate and slow categories with unique sequence motifs. We conclude that dephosphorylation initiated by the selective proteolysis of cyclin B drives the bulk of changes observed during mitotic exit.
HostingRepository	PRIDE
AnnounceDate	2020-09-04
AnnouncementXML	Submission_2020-09-04_04:14:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Holder
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-15 07:24:43	ID requested
⏵ 1	2020-09-04 04:14:41	announced
2	2023-11-14 08:50:53	announced	2023-11-14: Updated project metadata.

10.7554/eLife.59885;

submitter keyword: mitosis, mitotic exit, cell cycle, dephosphorylation, phospho-proteomics

Francis Barr
contact affiliation	Department of Biochemistry, University of Oxford
contact email	francis.barr@bioch.ox.ac.uk
lab head
James Holder
contact affiliation	University of Oxford
contact email	james.holder@path.ox.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/2020/09/PXD019788

PRIDE project URI

• PRIDE
  1. PXD019788
     1. Label: PRIDE project
     2. Name: Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit