Deleted in Colorectal Cancer Inhibits Protein Synthesis, But How?

Abstract

Deleted in colorectal cancer (DCC) is a chemotropic transmembrane receptor known to regulate neuron growth by stimulating or suppressing protein synthesis machinery. DCC does this by sensing an extracellular signal known as netrin‐1. In the absence of netrin‐1, DCC tethers translation machinery with its cytoplasmic tail (C‐tail), blocking ribosome function. In the presence of netrin‐1, DCC homodimerizes, releasing the translation machinery for local protein synthesis. While netrin‐1’s role is understood, the C‐tail‐translational machinery complex is poorly defined. Our lab focuses on which portion of the DCC C‐tail is necessary and sufficient at regulating protein synthesis. Using site‐directed mutagenesis, traditional cloning, and recombinant protein expression we have created a series of C‐tail truncation mutants. We measured the inhibitory function of each mutant using an in vitro luciferase assay. Our results indicate that the inhibitory region of the tail lies toward the N‐terminus. By defining the inhibitory portion of the C‐tail we have developed a model for how it is interacting with the translation machinery. Collectively, our data contribute to a growing body of knowledge about the relationship between chemotropism and protein synthesis.Support or Funding InformationResearch reported in this poster was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R15GM134393. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Support was also provided by an undergraduate research grant to E.A Spear from the Metropolitan State University of Denver Undergraduate Research Program.