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PXD030423

PXD030423 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA super-enhancer regulated RNA-binding protein cascade drives pancreatic cancer
DescriptionPancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy in need of new therapeutic options. Using an unbiased analysis of super-enhancers (SEs) as sentinels of core genes involved in cell-specific function, we uncover a druggable SE-mediated RNA-binding protein (RBP) cascade that supports PDAC growth through enhanced mRNA translation. This cascade is driven by a SE associated with the RBP heterogeneous nuclear ribonucleoprotein F, which stabilizes protein arginine methyltransferase 1 (PRMT1) to, in turn, control the translational mediator ubiquitin-associated protein 2-like. All three of these genes and the regulatory SE are essential for PDAC growth and coordinately regulated by the Myc oncogene. In line with this, modulation of the RBP network by PRMT1 inhibition reveals a unique vulnerability in Myc-high PDAC patient organoids and markedly reduces tumor growth in vivo. Our study highlights a functional link between epigenetic regulation and mRNA translation and identifies components that comprise unexpected therapeutic targets for PDAC.
HostingRepositoryPRIDE
AnnounceDate2023-06-15
AnnouncementXMLSubmission_2023-06-15_02:32:57.797.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD030423
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJoleneDiedrich
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListdimethylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-12-15 08:13:00ID requested
12023-06-15 02:32:58announced
Publication List
10.6019/PXD030423;
Keyword List
submitter keyword: PRMT1,RNA-binding protein, Pancreatic cancer, super-enhancers, tumor growth
Contact List
Ronald M.Evans
contact affiliationGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
contact emailevans@salk.edu
lab head
JoleneDiedrich
contact affiliationSalk
contact emailjdiedrich@salk.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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