The Myc gene encodes a protein that broadly orchestrates the gene expression essential to metabolism. It is also among the most frequently mutated, overexpressed or otherwise dysregulated genes in cancer. Studies led by Ludwig Scientific Director Chi Van Dang have previously shown that Myc dysfunction alters cellular metabolism to fuel tumor growth and also has a profound impact on the circadian rhythms of cancer cells. In a study published in Cell Reports in November, Chi, his collaborator Amita Segal and colleagues showed that Myc’s role in linking metabolism to the biological clock holds true in fruit flies as firmly as it does in humans and their cancers. Overexpression of the Drosophila Myc protein (dMyc) significantly disrupted not only the metabolism of fruit flies, but their circadian behavior as well. The latter disruption was accompanied by the heightened expression of genes involved in circadian rhythms—cyc, tim, cry and cwo. Mutations that dialed down Myc activity similarly influenced drosophila circadian behaviors, but these could be reversed by the loss of a protein known as dMnt, which suppresses dMyc activity. The findings expose the deep evolutionary roots of Myc’s role in linking metabolism and the circadian clock.
This article appeared in the April 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).