PXD022556

PXD022556 is an original dataset announced via ProteomeXchange.

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

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.

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]

submitter keyword: Cancer, eifFA, MATRIX, Translatome,Rocaglate, pulse SILAC, Translate

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

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/2021/11/PXD022556

PRIDE project URI

• PRIDE
  1. PXD022556
     1. Label: PRIDE project
     2. Name: Translatome and Translation Machinery Remodeling by eIF4A Inhibitors Mediates Antitumor Potency.