PXD008316

PXD008316 is an original dataset announced via ProteomeXchange.

Title	Cyclin A/Cdk1 modulates Plk1 activity in prometaphase to regulate k-MT attachment stability
Description	The fidelity of chromosome segregation in mitosis is safeguarded by the precise regulation of kinetochore microtubule (k-MT) attachment stability. Previously, we demonstrated that Cyclin A/Cdk1 destabilizes k-MT attachments to promote faithful chromosome segregation. Here, we use quantitative phosphoproteomics to identify 156 Cyclin A/Cdk1 substrates in prometaphase. One Cyclin A/Cdk1 substrate is myosin phosphatase targeting subunit 1 (MYPT1), and we show that MYPT1 localization to kinetochores depends on Cyclin A/Cdk1 activity and that MYPT1 destabilizes k-MT attachments by negatively regulating Plk1 at kinetochores. Thus, Cyclin A/Cdk1 phosphorylation primes MYPT1 for Plk1 binding. Interestingly, priming of PBIP1 by Plk1 itself (self-priming) increased in MYPT1-depleted cells showing that MYPT1 provides a molecular link between the processes of Cdk1-dependent priming and self-priming of Plk1 substrates. These data demonstrate cross-regulation between Cyclin A/Cdk1-dependent and Plk1-dependent phosphorylation of substrates during mitosis to ensure efficient correction of k-MT attachment errors necessary for high mitotic fidelity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:42:28.264.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Adamo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2017-11-29 00:26:29	ID requested
1	2017-12-01 08:58:07	announced
⏵ 2	2024-10-22 04:42:30	announced	2024-10-22: Updated project metadata.

Dumitru AMG, Rusin SF, Clark AEM, Kettenbach AN, Compton DA, Cyclin A/Cdk1 modulates Plk1 activity in prometaphase to regulate kinetochore-microtubule attachment stability. Elife, 6():(2017) [pubmed]

10.7554/elife.29303;

curator keyword: Biological

submitter keyword: mitosis,Cdk1, Cylin A, Plk1

Arminja N. Kettenbach
contact affiliation	The Geisel School of Medicine at Dartmouth
contact email	Arminja.N.Kettenbach@dartmouth.edu
lab head
Mark Adamo
contact affiliation	Dartmouth College
contact email	mark.e.adamo@dartmouth.edu
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/2017/12/PXD008316

PRIDE project URI

• PRIDE
  1. PXD008316
     1. Label: PRIDE project
     2. Name: Cyclin A/Cdk1 modulates Plk1 activity in prometaphase to regulate k-MT attachment stability