Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G.

Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Research Abstract Details 

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Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Abstract Text:

Nathan J Moerke,Huseyin Aktas,Han Chen,Sonia Cantel,Mikhail Y Reibarkh,Amr Fahmy,John D Gross,Alexei Degterev,Junying Yuan,Michael Chorev,Jose A Halperin,Gerhard Wagner,

Assembly of the eIF4E/eIF4G complex has a central role in the regulation of gene expression at the level of translation initiation. This complex is regulated by the 4E-BPs, which compete with eIF4G for binding to eIF4E and which have tumor-suppressor activity. To pharmacologically mimic 4E-BP function we developed a high-throughput screening assay for identifying small-molecule inhibitors of the eIF4E/eIF4G interaction. The most potent compound identified, 4EGI-1, binds eIF4E, disrupts eIF4E/eIF4G association, and inhibits cap-dependent translation but not initiation factor-independent translation. While 4EGI-1 displaces eIF4G from eIF4E, it effectively enhances 4E-BP1 association both in vitro and in cells. 4EGI-1 inhibits cellular expression of oncogenic proteins encoded by weak mRNAs, exhibits activity against multiple cancer cell lines, and appears to have a preferential effect on transformed versus nontransformed cells. The identification of this compound provides a new tool for studying translational control and establishes a possible new strategy for cancer therapy.

Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Publishing Authors By Initials

NJ Moerke,H Aktas,H Chen,S Cantel,MY Reibarkh,A Fahmy,JD Gross,A Degterev,J Yuan,M Chorev,JA Halperin,G Wagner,

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Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cell

VOLUME: 128

Page Numbers: 257-67

Journal Abbreviation: Cell

ISSN: 0092-8674

DAY: 26

MONTH: Jan

YEAR: 2007

Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Information

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LANGUAGE: eng

NlmUniqueID: 413066

Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Keywords Mesh Terms:

KEYWORDS: Thiazoles

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Information

Substance Name: Thiazoles

Registry Number: 0

Grant and Affiliation Information for Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G.

AFFILIATION: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM47467

ACRONYM: GM

MEDLINETA: Cell

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