The Eisenman and Edgar labs have shown that Myc overexpression leads to in- creased cell size. Yet how Myc accelerates the production of the building blocks required for cells to grow bigger has been unclear.
Staff scientist Dr. Carla Grandori said she has spent 10 years looking for target genes whose expression is controlled by Myc.
"Bob discovered many years ago that Myc binds to DNA and activates expression of specific genes. We have identified many genes that are regulated by Myc," she said.
"Many are so called 'housekeeping' genes that provide metabolic enzymes or key players of the cell protein-production machinery, which makes sense, since we know that Myc drives cell growth. We also knew that Myc overexpression, as seen in tumor cells, leads to a dramatic increase in protein synthesis."
Not yet identified among these Myc targets, though, was a group of genes, called transfer RNA genes that act as carriers for the 20 amino acids that constitute the building blocks of proteins.
Based on this knowledge of Myc, "it made sense to examine whether Myc controls the expression of the genes required for protein synthesis," Grandori said.
In collaboration with Dr. Robert White's laboratory at the University of Glasgow, Grandori and research technician Celine Ngouenet found that Myc directly activates this important set of genes. Most significant about this discovery is that a pathway distinct from most other genes in the cell governs expression of these genes.
The bulk of cellular genes, including all those previously shown to be regulated by Myc, are first converted to RNA (a process known as transcription) by an enzyme called RNA polymerase II and are converted to proteins (a process known as translation). tRNA genes are controlled by a separate enzyme known as RNA polymerase III, and are not converted into proteins but function as RNAs.
Grandori speculates that the ability of Myc to act as a master regulator of cell growth, by impinging on different cellular transcription machinery, may give it power as a tumor-inducing protein.
"Carla's results reveal a new pathway through which Myc stimulates the growth of cells," Eisenman said.
"We had always thought of Myc as being a typical RNA polymerase II transcription factor - and indeed it is. However, now it shows a new side, that it can interact with RNA polymerase III and somehow stimulate its activity."