Abstract
Arginylation consists of addition of an extra arginine to an existing peptide chain, thus changing the de facto primary sequence as well as the surface change. This process is evolutionarily conserved and mainly mediated by arginyltransferase1 (Ate1). While earlier studies found that the overall arginylation activity often increases during stressing conditions including heat shock, oxidative stress, and injury, little is known about the role of arginylation or Ate1 in stress response. By using multiple types of eukaryotic cells as test models, we found that Ate1 is a pro‐apoptotic factor. Knockout of Ate1 in cells leads to a retardation of stress response and the diminish of apoptosis and cell death during exposure of high doses of various stressing factors including heat shock, oxidative and osmotic stress, and heavy metal. Oppositely, over‐expression of Ate1 leads to cell death. Intriguingly, we also found that the activity of arginylation is essential for the wellbeing of the cells during mitochondria‐dependent metabolism as well as nutrient‐deprivation. Our data suggests that arginylation is a global regulator for metabolism and stress response, and provides an explanation for the observed role of Ate1 in carcinogenesis and injury.
Grant Funding Source: NIGMS