PXD046039

PXD046039 is an original dataset announced via ProteomeXchange.

Title	Proteomic Analysis of a PLK1-Dependent, Cell Cycle Degradation Program
Description	Targeted protein degradation by the ubiquitin-proteasome system is an essential mechanism regulating cellular division. The kinase PLK1 coordinates protein degradation at the G2/M phase of the cell cycle by promoting the binding of substrates to the E3 ubiquitin ligase SCFβTrCP. However, the magnitude to which PLK1 shapes the mitotic proteome has not been characterized. Combining deep, quantitative proteomics with pharmacologic PLK1 inhibition (PLK1i), we identified more than 200 proteins whose abundances were increased by PLK1i at G2/M. We validate many new PLK1-regulated proteins, including several substrates of the cell cycle E3 SCFCyclin F, demonstrating that PLK1 promotes proteolysis through at least two distinct SCF-family E3 ligases. Further, we found that the protein kinase A anchoring protein AKAP2 is cell cycle regulated and that its mitotic degradation is dependent on the PLK1/βTrCP-signaling axis. Interactome analysis revealed that the strongest interactors of AKAP2 function in signaling networks regulating proliferation, including MAPK, AKT, and Hippo. Altogether, our data demonstrate that PLK1 coordinates a widespread program of protein breakdown at G2/M. We propose that dynamic proteolytic changes mediated by PLK1 integrate proliferative signals with the core cell cycle machinery during cell division. This has potential implications in malignancies where PLK1 is aberrantly regulated.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:40:07.147.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine Mills
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-10 11:45:11	ID requested
⏵ 1	2025-05-06 12:40:08	announced

Mouery RD, Lukasik K, Hsu C, Bonacci T, Bolhuis DL, Wang X, Mills CA, Toomer ED, Canterbury OG, Robertson KC, Branigan TB, Brown NG, Herring LE, Gupton SL, Emanuele MJ, Proteomic analysis reveals a PLK1-dependent G2/M degradation program and a role for AKAP2 in coordinating the mitotic cytoskeleton. Cell Rep, 43(8):114510(2024) [pubmed]

10.1016/j.celrep.2024.114510;

submitter keyword: degradation, PLK1, cell cycle,ubiquitin

Michael Emanuele
contact affiliation	Department of Pharmacology and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill
contact email	emanuele@email.unc.edu
lab head
Christine Mills
contact affiliation	University of North Carolina - Chapel Hill
contact email	allie.mills@unc.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/2025/05/PXD046039

PRIDE project URI

• PRIDE
  1. PXD046039
     1. Label: PRIDE project
     2. Name: Proteomic Analysis of a PLK1-Dependent, Cell Cycle Degradation Program