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Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin
Open accessAbstract
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.
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Cites
Altering chemosensitivity by modulating translation elongation
Robert, F., Carrier, M., Rawe, S., Chen, S., Lowe, S., & Pelletier, J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005428 · Cited by 90
Cited by
Ingolia, N. T., Lareau, L. F., & Weissman, J. S. (2011) · Cell · doi:10.1016/j.cell.2011.10.002 · Cited by 2,187
Ribosome-targeting antibiotics and mechanisms of bacterial resistance
Wilson, D. N. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3155 · Cited by 1,054
Weinberg, D. E., Shah, P., Eichhorn, S. W., Hussmann, J. A., Plotkin, J. B., & Bartel, D. P. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.043 · Cited by 392
Ribosome Footprint Profiling of Translation throughout the Genome
Ingolia, N. T. (2016) · Cell · doi:10.1016/j.cell.2016.02.066 · Cited by 409
Real-Time Imaging of Translation on Single mRNA Transcripts in Live Cells
Wang, C., Han, B., Zhou, R., & Zhuang, X. (2016) · Cell · doi:10.1016/j.cell.2016.04.040 · Cited by 359
Metadata
- Authors
- Schneider-Poetsch, T., Ju, J., Eyler, D. E., Dang, Y., Bhat, S., Merrick, W. C., Green, R., Shen, B., & Liu, J. O.
- Venue
- Nature Chemical Biology
- Published
- 2010-01-31
- Volume
- 6
- Issue
- 3
- Pages
- 209-217
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2095032938
- Cited by
- 1,014
- References
- 1
- FWCI
- 13.59
- Type
- journal article
- Language
- en
- Open access
- green
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- Schneider-Poetsch, T., Ju, J., Eyler, D. E., Dang, Y., Bhat, S., Merrick, W. C., Green, R., Shen, B., & Liu, J. O. (2010). Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nature Chemical Biology. https://doi.org/10.1038/nchembio.304
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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