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Eukaryotic Translation Initiation Factor 4G Is Targeted for Proteolytic Cleavage by Caspase 3 during Inhibition of Translation in Apoptotic Cells
Open accessAbstract
Although much is known about the multiple mechanisms which induce apoptosis, comparatively little is understood concerning the execution phase of apoptosis and the mechanism(s) of cell killing. Several reports have demonstrated that cellular translation is shut off during apoptosis; however, details of the mechanism of translation inhibition are lacking. Translation initiation factor 4G (eIF4G) is a crucial protein required for binding cellular mRNA to ribosomes and is known to be cleaved as the central part of the mechanism of host translation shutoff exerted by several animal viruses. Treatment of HeLa cells with the apoptosis inducers cisplatin and etoposide resulted in cleavage of eIF4G, and the extent of its cleavage correlated with the onset and extent of observed inhibition of cellular translation. The eIF4G-specific cleavage activity could be measured in cell lysates in vitro and was inhibited by the caspase inhibitor Ac-DEVD-CHO at nanomolar concentrations. A combination of in vivo and in vitro inhibitor studies suggest the involvement of one or more caspases in the activation and execution of eIF4G cleavage. Furthermore recombinant human caspase 3 was expressed in bacteria, and when incubated with HeLa cell lysates, was shown to produce the same eIF4G cleavage products as those observed in apoptotic cells. In addition, purified caspase 3 caused cleavage of purified eIF4G, demonstrating that eIF4G could serve as a substrate for caspase 3. Taken together, these data suggest that cellular translation is specifically inhibited during apoptosis by a mechanism involving cleavage of eIF4G, an event dependent on caspase activity.
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“eIF4G has caspase sites and can be cleaved by caspase-3 during apoptosis34.”
From Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer (2024) · cites this paper as [34]
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Metadata
- Authors
- Marissen, W. E., & Lloyd, R. E.
- Affiliations
- University of Oklahoma Health Sciences Center (US)
- Corresponding author
- Lloyd, Richard E.
- ORCID
- Lloyd, Richard E.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1998-12-01
- Volume
- 18
- Issue
- 12
- Pages
- 7565-7574
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC109337
- OpenAlex
- W2141571283
- Cited by
- 198
- References
- 42
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 5 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 11 · 2013: 6 · 2012: 8
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI027914, AI27914)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- eIF4G, caspase-3, apoptosis, protein synthesis inhibition, proteolytic cleavage, cisplatin, etoposide, Ac-DEVD-CHO, HeLa cells, translation initiation factors
- MeSH terms
- Amino Acid Chloromethyl Ketones, Cisplatin, Cytochrome c Group, Deoxyadenine Nucleotides, Etoposide, HeLa Cells, Humans, Kinetics, Oligopeptides, Peptide Initiation Factors, Protease Inhibitors, Recombinant Proteins, Protein Biosynthesis, Apoptosis, Caspases, Eukaryotic Initiation Factor-4G, Caspase 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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