Abstract 1123 Uncovering the role of Ate1 in the cell cycle

Arginyltransferase (Ate1) is an enzyme that catalyzes the post-translational addition of an arginine to a target protein or peptide, termed arginylation. Arginylation is an understudied yet emerging area of research that is involved in many essential processes in normal cells and pathologies. Recent reports suggest that Ate1 has a role in cell cycle regulation, but the mechanism is entirely unknown. Using basic biochemical techniques, we have found evidence showing that Ate1 may be an important regulator of several G1/S checkpoint proteins including cyclin D1, CDK4, and CDK6. Notably, Ate1 does not appear to regulate these proteins via mRNA, indicating a post-translational mechanism may be involved. Particularly, Ate1 appears to affect the steady-state level of these proteins by promoting their degradation. As such, these proteins demonstrate a significant increase in half-life when Ate1 is not present. Future studies will uncover the exact underlying mechanism, including which proteins may be arginylated, leading to G1/S checkpoint slippage in cells lacking Ate1. This research was supported by NIGMS: R01GM138557.