Minimizing Protein Synthesis Inhibits the Myc Oncogene

Cancer researchers have found a way to reverse the oncogenic effects of the mutated Myc oncogene by enforcing strict control on the level of cellular protein production.

The protein encoded by the Myc gene is a multifunctional, nuclear phosphoprotein that plays a role in cell-cycle progression, apoptosis, and cellular transformation. It functions as a transcription factor that regulates transcription of specific target genes. Mutations, overexpression, rearrangement, and translocation of this gene have been associated with a variety of hematopoietic tumors, leukemias, and lymphomas, including Burkitt lymphoma.

In the current study investigators at the University of California, San Francisco (USA) crossed two genetically engineered lines of mice. One line overexpressed Myc and was prone to cancer development. The other line was modified to synthesize protein at the most minimal level.

Results published in the December 18, 2008, issue of the journal Nature revealed that heterozygotic offspring resulting from crossing the two genetically engineered strains of mice expressed Myc. Nonetheless, these animals were able to restrain protein production. These mice displayed near-normal cell growth and division, and the ability to enter apoptosis that is needed to counter cancer.

"We discovered a previously unrecognized link between alterations in protein synthesis and the mechanism by which cells maintain the integrity of the genome," said senior author Dr. Davide Ruggero, assistant professor of urology at the University of California, San Francisco. "We found that when Myc is overexpressed, this leads to changes in protein levels of a key gene that is essential for normal distribution of genetic material between daughter cells during cell division. Control of protein production rapidly affects cell behavior, and in a robust manner. The ability of the Myc oncogene to directly alter this process may well explain the rapid progression of cancer formation."

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