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Phosphorylation of the proto-oncogene product eukaryotic initiation factor 4E is a common cellular response to tumor
M W Marino1, L J Feld, E A Jaffe
1Memorial Sloan-Kettering Cancer Center, New York, New York.
Abstract:
The initiation of mRNA translation is regulated by the reversible phosphorylation of several initiation factors. We report here that tumor necrosis factor-alpha (TNF) rapidly stimulates phosphorylation of one such factor, an mRNA cap binding protein, in several cell types which are important in vitro models of TNF action. This protein has been purified, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor 4E. These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the various actions of TNF in diverse cell types.
Insights
Tumor necrosis factor-alpha (TNF) triggers rapid phosphorylation of eukaryotic initiation factor 4E, a key mRNA cap-binding protein. This early event impacts cellular translation and is crucial for TNF
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- mRNA translation initiation is a critical regulatory step controlled by the phosphorylation of initiation factors.
- Tumor necrosis factor-alpha (TNF) is a cytokine with diverse cellular functions, many of which are initiated early in cellular responses.
Purpose of the Study:
- To investigate the effect of TNF on the phosphorylation of mRNA translation initiation factors.
- To identify the specific protein targeted by TNF-induced phosphorylation during translation initiation.
Main Methods:
- Utilized various cell types as in vitro models for TNF action.
- Purified, sequenced, and identified the specific mRNA cap-binding protein affected by TNF.
- Analyzed the phosphorylation status of the identified protein in response to TNF stimulation.
Main Results:
- TNF rapidly stimulates the phosphorylation of an mRNA cap-binding protein in multiple cell types.
- The phosphorylated protein was identified as eukaryotic initiation factor 4E (eIF4E), a proto-oncogene product.
- Phosphorylation of eIF4E is an early and common event in diverse TNF-mediated cellular actions.
Conclusions:
- TNF-induced phosphorylation of eukaryotic initiation factor 4E is a significant early event in cellular responses.
- This post-translational modification of a key translation factor highlights a mechanism by which TNF regulates protein synthesis.
- The findings provide insights into the molecular pathways linking TNF signaling to cellular processes.