Rocaglates Induce Gain-of-Function Alterations to eIF4A and eIF4F

• DOI: 10.1016/j.celrep.2020.02.002
• Publication Date: 2020-02-25T15:58:20Z
• Authors: Jennifer Chu; Wenhan Zhang; Regina Cencic; Patrick B.F. O’Co...; Francis Robert; William G. Devine; Asher Selznick; Thomas Henkel; William C. Merrick; Lauren E. Brown; Pavel V. Baranov; John A. Porco; Jerry Pelletier
• Keywords: eIF4A; Gain of function; Mechanism of Action

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