PXD044854

PXD044854 is an original dataset announced via ProteomeXchange.

Title	The protein phosphatase-2A subunit PR130 is linked to cytotoxic protein aggregate formation in mesenchymal pancreatic ductal adenocarcinoma cells
Description	Protein phosphatase-2A (PP2A) is a major source of cellular serine/threonine phosphatase activity. PP2A B-type subunits regulate the cellular localization and activity of catalytically active PP2A-A/PP2A-C complexes towards individual PP2A targets. Despite ample knowledge on PP2A, there is limited knowledge on how PP2A B-type subunits regulate specific cellular functions. We show that mesenchymal pancreatic ductal adenocarcinoma (PDAC) cells have significantly higher expression levels of the PP2A B-type subunit PR130/PPP2R3A than epithelial PDAC cells. The higher levels of PR130 are linked to a cell-type selective vulnerability of mesenchymal PDAC cells to the PP2A inhibitor phendione. Phendione induces apoptosis and an accumulation of cytotoxic protein aggregates in such cells. Proteomic analyses reveal a specific upregulation of the chaperone heat shock protein HSP70 by phendione in mesenchymal PDAC cells. Inhibition of HSP70 promotes phendione-induced tumor cell death. We additionally disclose that phendione promotes a proteasomal degradation of PR130 in mesenchymal PDAC cells. Genetic elimination of PR130 sensitizes such cells to phendione-induced apoptosis and protein aggregate formation. These data illustrate pharmacologically amenable, selective dependencies of mesenchymal PDAC cells on PP2A-PR130 and HSP70. PP2A inhibitors trigger a harmful accumulation of protein aggregates in neurons. We provide evidence on how this can be exploited to kill mesenchymal tumor cells.
HostingRepository	PRIDE
AnnounceDate	2024-05-22
AnnouncementXML	Submission_2024-05-22_02:47:17.593.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	F Butter
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-25 04:23:27	ID requested
⏵ 1	2024-05-22 02:47:18	announced

Nguyen A, Mustafa AM, Leydecker AK, Halilovic M, Murr J, Butter F, Kr, ä, mer OH, The protein phosphatase-2A subunit PR130 is involved in the formation of cytotoxic protein aggregates in pancreatic ductal adenocarcinoma cells. Cell Commun Signal, 22(1):217(2024) [pubmed]

10.1186/s12964-024-01597-8;

submitter keyword: LC-MS/MS

Falk Butter
contact affiliation	Institute of Molecular Biology (IMB)
contact email	f.butter@imb.de
lab head
F Butter
contact affiliation	Quantitative Proteomics Institute of Molecular Biology (IMB)
contact email	f.butter@imb-mainz.de
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/2024/05/PXD044854

PRIDE project URI

• PRIDE
  1. PXD044854
     1. Label: PRIDE project
     2. Name: The protein phosphatase-2A subunit PR130 is linked to cytotoxic protein aggregate formation in mesenchymal pancreatic ductal adenocarcinoma cells