PXD044854 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-08-25 04:23:27 | ID requested | |
⏵ 1 | 2024-05-22 02:47:18 | announced | |
Publication List
Nguyen A, Mustafa AM, Leydecker AK, Halilovic M, Murr J, Butter F, Kr, รค, 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; |
Keyword List
submitter keyword: LC-MS/MS |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD044854
- Label: PRIDE project
- Name: The protein phosphatase-2A subunit PR130 is linked to cytotoxic protein aggregate formation in mesenchymal pancreatic ductal adenocarcinoma cells