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Overexpression of eukaryotic protein synthesis initiation factor 4E in HeLa cells results in aberrant growth and morphology.
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , |
| In: | Proceedings of the National Academy of Sciences, 87, 1990, 21, S. 8212-8216 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>Eukaryotic protein synthesis initiation factor 4E (eIF-4E) is a 25-kDa polypeptide that binds to the 7-methylguanosine-containing cap of mRNA and participates in the transfer of mRNA to the 40S ribosomal subunit, a step that is rate-limiting for protein synthesis under most cellular conditions. eIF-4E is the least abundant of the initiation factors, is present at approximately 10% of molar concentration of mRNA, and thus may serve as a site of regulation for the recruitment of mRNA into polysomes. Previous studies have indicated that phosphorylation of eIF-4E at Ser-53 is correlated with an increased rate of protein synthesis in a variety of systems in vivo and is required for eIF-4E to become bound to the 48S initiation complex. In this study we show that overexpression of eIF-4E in HeLa cells using an episomally replicating, BK virus-based vector leads to an unusual phenotype: cells grow rapidly, forming densely packed, multilayered foci. They progressively form syncytia, some containing as many as six nuclei, and ultimately lyse 1 month after transfection. Some of these properties are reminiscent of oncogenically transformed cells. Cells transfected with the identical vector expressing a variant of eIF-4E, which contains alanine at position 53 and thus cannot be phosphorylated at the major in vivo site, grow normally. Estimations using the Ala-53 variant or a bacterial chloramphenicol acetyltransferase reporter gene in the same vector indicate that the degree of eIF-4E overexpression is 3- to 9-fold more than the endogenous level. These results suggest that eIF-4E may play a key role in cell cycle progression.</jats:p> |
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| Umfang: | 8212-8216 |
| ISSN: |
1091-6490
0027-8424 |
| DOI: | 10.1073/pnas.87.21.8212 |