Dataset Information

Proteome profiling followng targeting eIF4E

ABSTRACT: Here we have compared the impact of loss the protein synthesis initiation factor eIF4e in non samll cell lung cancer cells. Expression of eIF4E was targeted by an eIF4E siRNA or by expressiojn of eIF4E-dTAG construct allowing degradation of eIF4e-dTAG with the heterobifunctional dTAGv-1 small molecule. Proteomes were profiled following 72 hr exposure of the four H1299 eIF4E-dTAG clones (C2-2, C3-1, N2-1 and N3-2) to 0.5 microM dTAGV-1 or H1299 parent cells transfected with 1 microg eIF4E siRNA (siTOOLS, Planegg, Germany) using Lipofectamine 3000 transfection reagent (Fisher Scientific, cat#L3000008).

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Permanent Cell Line Cell

DISEASE(S): Non-small Cell Lung Carcinoma

SUBMITTER: Paul Clarke

LAB HEAD: Paul Andrew Clarke

PROVIDER: PXD057122 | Pride | 2025-05-07

REPOSITORIES: Pride

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Publications

Integrating fragment-based screening with targeted protein degradation and genetic rescue to explore eIF4E function.

Sharp Swee Y SY Martella Marianna M D'Agostino Sabrina S Milton Christopher I CI Ward George G Woodhead Andrew J AJ Richardson Caroline J CJ Carr Maria G MG Chiarparin Elisabetta E Cons Benjamin D BD Coyle Joseph J East Charlotte E CE Hiscock Steven D SD Martinez-Fleites Carlos C Mortenson Paul N PN Palmer Nick N Pathuri Puja P Powers Marissa V MV Saalau Susanne M SM St Denis Jeffrey D JD Swabey Kate K Vinković Mladen M Walton Hugh H Williams Glyn G Clarke Paul A PA

Nature communications 20241120 1

Eukaryotic initiation factor 4E (eIF4E) serves as a regulatory hub for oncogene-driven protein synthesis and is considered a promising anticancer target. Here we screen a fragment library against eIF4E and identify a ligand-binding site with previously unknown function. Follow-up structure-based design yields a low nM tool compound (4, K<sub>d</sub> = 0.09 µM; LE 0.38), which disrupts the eIF4E:eIF4G interaction, inhibits translation in cell lysates, and demonstrates target engagement with eIF4E ...[more]

PMID: 40016190

			Action	DRS
	20230626_201715_0754_hsa.sne	Other
	22P03810001.raw	Raw
	22P03810002.raw	Raw
	22P03810003.raw	Raw
	22P03810004.raw	Raw

Dataset Information

Proteome profiling followng targeting eIF4E

Dataset's files

Publications

Integrating fragment-based screening with targeted protein degradation and genetic rescue to explore eIF4E function.

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