Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E.
- 6 February 1996
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 93 (3), 1065-1070
- https://doi.org/10.1073/pnas.93.3.1065
Abstract
The structure of m7GpppN (where N is any nucleotide), termed cap, is present at the 5' end of all eukaryotic cellular mRNAs (except organellar). The eukaryotic initiation factor 4E (eIF-4E) binds to the cap and facilitates the formation of translation initiation complexes. eIF-4E is implicated in control of cell growth, as its overexpression causes malignant transformation of rodent cells and deregulates HeLa cell growth. It was suggested that overexpression of eIF-4E results in the enhanced translation of poorly translated mRNAs that encode growth-promoting proteins. Indeed, enhanced expression of several proteins, including cyclin D1 and ornithine decarboxylase (ODC), was documented in eIF-4E-overexpressing NTH 3T3 cells. However, the mechanism underlying this increase has not been elucidated. Here, we studied the mode by which eIF-4E increases the expression of cyclin D1 and ODC. We show that the increase in the amount of cyclin D1 and ODC is directly proportional to the degree of eIF-4E overexpression. Two mechanisms, which are not mutually exclusive, are responsible for the increase. In eIF-4E-overexpressing cells the rate of translation initiation of ODC mRNA was increased inasmuch as the mRNA sedimented with heavier polysomes. For cyclin D1 mRNA, translation initiation was not increased, but rather its amount in the cytoplasm increased, without a significant increase in total mRNA. Whereas, in the parental NIH 3T3 cell line, a large proportion of the cyclin D1 mRNA was confined to the nucleus, in eIF-4E-overexpressing cells the vast majority of the mRNA was present in the cytoplasm. These results indicate that eIF-4E affects directly or indirectly mRNA nucleocytoplasmic transport, in addition to its role in translation initiation.Keywords
This publication has 42 references indexed in Scilit:
- A nuclear cap binding protein complex involved in pre-mRNA splicingCell, 1994
- Translation factors as effectors of cell growth and tumorigenesisCurrent Opinion in Cell Biology, 1993
- Decreasing the level of translation initiation factor 4E with antisense rna causes reversal of ras‐mediated transformation and tumorigenesis of cloned rat embryo fibroblastsInternational Journal of Cancer, 1993
- Ornithine decarboxylase activity is critical for cell transformationNature, 1992
- A cap binding protein that may mediate nuclear export of RNA polymerase II-transcribed RNAs.The Journal of cell biology, 1992
- Cap recap: The involvement of eIF-4F in regulating gene expressionCell, 1992
- Adenovirus inhibition of cellular protein synthesis involves inactivation of cap-binding proteinCell, 1991
- Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' capNature, 1990
- mRNA cap binding proteins: essential factors for initiating translationCell, 1985
- Inhibition of HeLa cell protein synthesis during adenovirus infectionJournal of Molecular Biology, 1979