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Malignant transformation by the eukaryotic translation initiation factor 3 subunit p48 (eIF3e).
Greg L Mayeur1, John W B Hershey
1Department of Biological Chemistry, School of Medicine, University of California, Davis, CA 95616, USA.
FEBS Letters
|March 21, 2002
Summary
A truncated eukaryotic initiation factor-3e (eIF3e) protein, encoded by the Int6 gene, causes malignant transformation in cells. Full-length eIF3e does not induce transformation, indicating a specific role for the truncated form in cancer development.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Translation initiation factors like eIF4E and PKR are linked to cancer.
- The Int6 gene encodes the p48 e-subunit of mammalian eukaryotic initiation factor 3 (eIF3).
- Mouse mammary tumor virus integration at Int6 can produce truncated eIF3e.
Purpose of the Study:
- To investigate the role of truncated eIF3e in cellular transformation.
- To determine if full-length eIF3e has similar transforming effects.
- To assess the impact of truncated eIF3e on apoptosis.
Main Methods:
- Stable expression of truncated and full-length eIF3e in NIH 3T3 cells.
- Assessing malignant transformation criteria: foci formation, anchorage-independent growth, accelerated growth, and loss of contact inhibition.
- Evaluating the effect of truncated eIF3e on serum starvation-induced apoptosis.
Main Results:
- Stable expression of truncated eIF3e induced malignant transformation in NIH 3T3 cells.
- Transformation was evidenced by foci formation, anchorage-independent growth, accelerated proliferation, and lack of contact inhibition.
- Full-length eIF3e expression did not lead to transformation.
- Truncated eIF3e inhibited apoptosis induced by serum starvation.
Conclusions:
- The truncated form of eIF3e, but not the full-length protein, possesses oncogenic properties.
- Truncated eIF3e contributes to cellular transformation and inhibits apoptosis, suggesting its potential role in cancer progression.
- The Int6 gene and its truncated product are significant in understanding cancer development mechanisms.