Overexpression of eukaryotic protein synthesis initiation factor 4E in HeLa cells results in aberrant growth and morphology
- PMID: 2122455
- PMCID: PMC54925
- DOI: 10.1073/pnas.87.21.8212
Overexpression of eukaryotic protein synthesis initiation factor 4E in HeLa cells results in aberrant growth and morphology
Abstract
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.
Similar articles
-
Translational regulation of the mammalian growth-related protein P23: involvement of eIF-4E.Cell Mol Biol Res. 1994;40(7-8):633-41. Cell Mol Biol Res. 1994. PMID: 7787881
-
Characterization of wild-type and Ser53 mutant eukaryotic initiation factor 4E overexpression in mammalian cells.J Biol Chem. 1993 Jun 5;268(16):11902-9. J Biol Chem. 1993. PMID: 8505316
-
Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E.Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1065-70. doi: 10.1073/pnas.93.3.1065. Proc Natl Acad Sci U S A. 1996. PMID: 8577715 Free PMC article.
-
Cap binding complexes and cellular growth control.Biochimie. 1995;77(1-2):40-4. doi: 10.1016/0300-9084(96)88102-8. Biochimie. 1995. PMID: 7599274 Review.
-
Participation of initiation factors in the recruitment of mRNA to ribosomes.Biochimie. 1994;76(9):831-8. doi: 10.1016/0300-9084(94)90184-8. Biochimie. 1994. PMID: 7880899 Review.
Cited by
-
Phosphorylation of eIF4E Confers Resistance to Cellular Stress and DNA-Damaging Agents through an Interaction with 4E-T: A Rationale for Novel Therapeutic Approaches.PLoS One. 2015 Apr 29;10(4):e0123352. doi: 10.1371/journal.pone.0123352. eCollection 2015. PLoS One. 2015. PMID: 25923732 Free PMC article.
-
Cell cycle progression and proliferation despite 4BP-1 dephosphorylation.Mol Cell Biol. 1999 Sep;19(9):6041-7. doi: 10.1128/MCB.19.9.6041. Mol Cell Biol. 1999. PMID: 10454551 Free PMC article.
-
A model for co-expression pattern analysis of genes implicated in angiogenesis and tumour cell invasion in cervical cancer.Br J Cancer. 2002 Aug 27;87(5):537-44. doi: 10.1038/sj.bjc.6600471. Br J Cancer. 2002. PMID: 12189553 Free PMC article.
-
Overexpression of initiation factor eIF-4E does not relieve the translational repression of ribosomal protein mRNAs in quiescent cells.Gene Expr. 1995;4(4-5):241-52. Gene Expr. 1995. PMID: 7787416 Free PMC article.
-
Differential expression of vascular endothelial growth factor mRNA vs protein isoform expression in human breast cancer and relationship to eIF-4E.Br J Cancer. 1998 Jun;77(12):2120-8. doi: 10.1038/bjc.1998.356. Br J Cancer. 1998. PMID: 9649123 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous