Inhibition of Eukaryotic Translation Elongation by Cycloheximide and Lactimidomycin

By Tilman Schneider-Poetsch, J. Ju, D. Eyler, Yongjun Dang, S. Bhat, W. Merrick, R. Green, B. Shen, Jun O. Liu. Nature Chemical Biology, 2010

994 citations recorded by the source corpus.

Although the protein synthesis inhibitor cycloheximide (CHX) has been known for decades, its precise mechanism of action remains incompletely understood. The glutarimide portion of CHX is seen in a family of structurally related natural products including migrastatin, isomigrastatin and lactimidomycin (LTM). LTM, isomigrastatin and analogs were found to have a potent antiproliferative effect on tumor cell lines and selectively inhibit protein translation. A systematic comparative study of the effects of CHX and LTM on protein translation revealed both similarities and differences between the two inhibitors. Both LTM and CHX were found to block the translocation step in elongation. Footprinting experiments revealed protection of a single cytidine nucleotide (C3993) in the E-site of the 60S ribosomal subunit, defining a common binding pocket for both inhibitors in the ribosome. These results shed new light on the molecular mechanism of inhibition of translation elongation by both CHX and LTM.

Subfields: Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/fb6f40e23af5b09f49bf76cd49ccfdf2e0127d49

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Pharmacology

Jonathan S. Weissman

Citations in the corpus

Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes (2011, methodology): “We compared cycloheximide (Schneider-Poetsch et al., 2010) and emetine pretreatment to a ‘‘no drug’’ approach in which unperturbed cells were lysed in a buffer that should not support continued elongation.”