PXD056390

PXD056390 is an original dataset announced via ProteomeXchange.

Title	A chemical-genetic system to rapidly inhibit the PP2A-B56 phosphatase
Description	Serine-threonine phosphatases have been challenging to study because of the lack of specific inhibitors. Their catalytic domains are druggable, but these are shared or very similar between individual phosphatase complexes, precluding their specific inhibition. Instead, phosphatase complexes achieve specificity by interacting with short-linear motifs (SLiMs) in substrates or their binding partners. We develop here a chemical-genetic system to rapidly inhibit these interactions within the PP2A-B56 family. Drug-inducible recruitment of ectopic SLiMs (“directSLiMs”) is used to rapidly block the SLiM-binding pocket on the B56 regulatory subunit, thereby displacing endogenous interactors and inhibiting PP2A-B56 activity within seconds. We use this system to characterise PP2A-B56 substrates during mitosis and to identify a novel role for PP2A-B56 in maintaining kinetochore microtubule attachments at metaphase. The directSLiMs approach can be used to inhibit any other phosphatase, enzyme or protein that uses a critical SLiM-binding interface, providing a powerful strategy to inhibit and characterise proteins once considered “undruggable”.
HostingRepository	PRIDE
AnnounceDate	2025-02-06
AnnouncementXML	Submission_2025-02-06_08:10:43.085.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juan Manuel Valverde
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-30 05:58:47	ID requested
⏵ 1	2025-02-06 08:10:43	announced

Dataset with its publication pending

submitter keyword: phosphoproteomics, phosphatase, phosphorylation, PP2A-B56

Adrian Saurin
contact affiliation	Cellular and Systems Medicine, Jacqui Wood Cancer Centre, School of Medicine, University of Dundee, Dundee. DD1 9SY, UK
contact email	a.suarin@dundee.ac.uk
lab head
Juan Manuel Valverde
contact affiliation	University of Dundee
contact email	jvalverde001@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056390
     1. Label: PRIDE project
     2. Name: A chemical-genetic system to rapidly inhibit the PP2A-B56 phosphatase