PXD052317-1

PXD052317 is an original dataset announced via ProteomeXchange.

Title	PPP1R2 (Inhibitor 2) stimulates protein phosphatase PP1 through stabilisation of dynamic subunit interactions
Description	Protein Ser/Thr phosphatase PP1 is always associated with one or two regulatory subunits or RIPPOs. One of the earliest evolved RIPPOs is PPP1R2, also known as Inhibitor-2. Since its discovery nearly 5 decades ago, PPP1R2 has been variously described as an inhibitor, activator or (metal) chaperone of PP1, but it is still unknown how PPP1R2 affects the function of PP1 in intact cells. Here, using newly developed research tools, we demonstrate that PPP1R2 stabilizes a subgroup of PP1 holoenzymes, exemplified by PP1:RepoMan, thereby promoting the dephosphorylation of their substrates. Mechanistically, the recruitment of PPP1R2 disrupts the inhibitory, fuzzy interaction between the C-terminal tail and catalytic domain of PP1, and generates an additional C-terminal RepoMan-interaction site. The resulting holoenzyme is further stabilized by a direct PPP1R2:RepoMan interaction, which renders it refractory to competitive disruption by RIPPOs that do not interact with PPP1R2. Our data demonstrate that PPP1R2 modulates the function of PP1 by altering the balance between holoenzymes through stabilisation of specific subunit interactions.
HostingRepository	PRIDE
AnnounceDate	2024-11-13
AnnouncementXML	Submission_2024-11-13_11:45:54.512.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD052317
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Rita Derua
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-16 07:05:16	ID requested
⏵ 1	2024-11-13 11:45:54	announced

10.1038/S41467-024-54256-4;

10.6019/PXD052317;

submitter keyword: PP1, holoenzyme, PPP1R2

Prof. Dr. Mathieu Bollen
contact affiliation	Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium.
contact email	mathieu.bollen@kuleuven.be
lab head
Rita Derua
contact affiliation	KU Leuven
contact email	rita.derua@kuleuven.be
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/2024/11/PXD052317

PRIDE project URI

• PRIDE
  1. PXD052317
     1. Label: PRIDE project
     2. Name: PPP1R2 (Inhibitor 2) stimulates protein phosphatase PP1 through stabilisation of dynamic subunit interactions