Rocaglates Induce Gain-of-Function Alterations to EIF4A and EIF4F

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2020 Feb 27

PMID 32101697

Citations 43

Authors

Jennifer Chu

Wenhan Zhang

Regina Cencic

Patrick B F OConnor

Francis Robert

William G Devine

Asher Selznick

Thomas Henkel

William C Merrick

Lauren E Brown

Pavel V Baranov

John A Porco Jr

Jerry Pelletier

Affiliations

Soon will be listed here.

Abstract

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action. Here, we present a comprehensive study comparing the biological activities of >200 rocaglates to better understand how the presence of different chemical entities influences their biological activities. Through this, we find that most rocaglates preferentially repress the translation of mRNAs containing purine-rich 5' leaders, but certain rocaglates lack this bias in translation repression. We also uncover an aspect of rocaglate mechanism of action in which the pool of translationally active eIF4F is diminished due to the sequestration of the complex onto RNA.

Citing Articles

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