Phosphorylation of a Translation Initiation Factor Drives Tumor Development

A team of Canadian cancer researchers have found a link between the development of prostate cancer and the phosphorylation of eIF4E, the mRNA 5′ cap-binding protein.

The eIF4E (eukaryotic translation initiation factor 4E) polypeptide is a 24-kDa molecular weight polypeptide that exists as both a free form and as part of a multiprotein complex termed eIF4F. The eIF4E peptide is the rate-limiting component of the eukaryotic translation apparatus and is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis. eIF4E's function is to bind an mRNA cap and ultimately bring it to the ribosome.

Previous studies have shown that aberrant expression of eIF4E promotes tumorigenesis, and has been implicated in cancer development and progression. Since eIF4E expression is regulated by phosphorylation, investigators at McGill University (Montreal, Canada) and the University of Montreal (Canada) genetically engineered a line of mice with a variant form of eIF4E in their prostate tissue that was not susceptible to regulation by phosphorylation.

They reported in the August 2, 2010, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS) that the genetically engineered mice were resistant to prostate cancer tumorigenesis. By using a genome-wide analysis of translated mRNAs, they showed that the phosphorylation of eIF4E was required for translational up-regulation of several proteins implicated in tumorigenesis. Accordingly, increased phospho-eIF4E levels correlated with disease progression in patients with prostate cancer.

The investigators concluded by saying, "Our findings establish eIF4E phosphorylation as a critical event in tumorigenesis. These findings raise the possibility that chemical compounds that prevent the phosphorylation of eIF4E could act as anticancer drugs.”

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