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Translation initiation factors induce DNA synthesis and transform NIH 3T3 cells
M R Smith1, M Jaramillo, Y L Liu
1Biological Carcinogenesis and Development Program, National Cancer Institute, Frederick Cancer Research Facility, MD 21701.
The New Biologist
|July 1, 1990
Summary
Translation initiation factors, eukaryotic initiation factor 4E (eIF-4E) and eIF-4F, promote cell growth and transformation when introduced into NIH 3T3 cells. These findings identify new proto-oncogenes involved in protein synthesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Protein synthesis initiation involves polypeptide factors binding to eukaryotic mRNAs.
- These factors facilitate the formation of ribosome initiation complexes, a critical step in translation.
Purpose of the Study:
- To investigate the potential growth-promoting role of mRNA-binding translation initiation factors in living cells.
- To determine if these factors can induce DNA synthesis and cellular transformation.
Main Methods:
- Microinjection of purified recombinant eukaryotic initiation factor 4E (eIF-4E) and rabbit reticulocyte eIF-4F into quiescent NIH 3T3 cells.
- Observation and quantification of DNA synthesis and morphological changes in treated cells.
Main Results:
- Recombinant eIF-4E and eIF-4F induced a dose-dependent increase in DNA synthesis.
- Microinjected factors caused morphological transformation of NIH 3T3 cells, indicative of oncogenic potential.
Conclusions:
- Polypeptides activating the rate-limiting step of protein synthesis can be mitogenic and oncogenic upon overexpression.
- eIF-4E and eIF-4F represent a novel class of cytoplasmic proto-oncogenic proteins involved in translation initiation.