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PXD022556

PXD022556 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTranslatome and Translation Machinery Remodeling by eIF4A Inhibitors Mediates Antitumor Potency.
DescriptionProtein synthesis-targeting agents against eIF4A activity, including rocaglates, are actively pursued as anticancer and antiviral therapies. Yet, their full effect on the translational landscape is unknown, especially with regards to up-regulated proteins and drug-activated translation factors that mediate rocaglates’ remarkable anticancer potency. Here, we investigated rocaglate-driven global translational remodeling in cancer cells. Proteomic translatome analysis by TMT-pulse-SILAC revealed an extensive repertoire of rocaglate-inducible proteins that regulate hitherto unrecognized mechanisms of cytotoxicity. As proof-of-concept, we show that GEF-H1 induction activates anti-survival RHOA/JNK signaling. Intriguingly, rocaglate responses persist in eIF4A-depleted cells. Global MATRIX survey of translation machinery adaptations to rocaglates revealed augmented translational activities of the general translation factor eEF1ε1, and the DEAD-box RNA helicase DDX17, which drive rocaglate-specific protein induction and drug response. This original unbiased proteomic interrogation of rocaglate-driven translational reprogramming transforms the current definition of rocaglates as one-dimensional eIF4A inhibitors to comprehensive remodelers of the protein synthesis landscape.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:30:22.965.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD022556
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJonathan Krieger
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-11-16 03:39:42ID requested
12021-11-23 08:49:27announced
22024-10-22 05:30:23announced2024-10-22: Updated project metadata.
Publication List
10.6019/PXD022556;
10.1016/j.celrep.2021.109806;
Ho JJD, Cunningham TA, Manara P, Coughlin CA, Arumov A, Roberts ER, Osteen A, Kumar P, Bilbao D, Krieger JR, Lee S, Schatz JH, Proteomics reveal cap-dependent translation inhibitors remodel the translation machinery and translatome. Cell Rep, 37(2):109806(2021) [pubmed]
Keyword List
submitter keyword: Cancer, eifFA, MATRIX, Translatome,Rocaglate, pulse SILAC, Translate
Contact List
Jonathan H. Schatz
contact affiliationDepartment of Urology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
contact emailjschatz@med.miami.edu
lab head
Jonathan Krieger
contact affiliationBruker
contact emailJRKrieger@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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