PXD022556 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Translatome and Translation Machinery Remodeling by eIF4A Inhibitors Mediates Antitumor Potency. |
Description | Protein 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:30:22.965.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD022556 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Jonathan Krieger |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-11-16 03:39:42 | ID requested | |
1 | 2021-11-23 08:49:27 | announced | |
⏵ 2 | 2024-10-22 05:30:23 | announced | 2024-10-22: 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 affiliation | Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA |
contact email | jschatz@med.miami.edu |
lab head | |
Jonathan Krieger |
contact affiliation | Bruker |
contact email | JRKrieger@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022556
- Label: PRIDE project
- Name: Translatome and Translation Machinery Remodeling by eIF4A Inhibitors Mediates Antitumor Potency.