What is it about?

To function properly within a tissue, cells must maintain a balance of protein synthesis, folding, and degradation. When cells undergo stress and fall out of balance, the cells activate a stress response. In some ways, these stress responses are a double-edged sword. A short-lived or mild activation of stress is beneficial for the survival and functional health of most cells; however, strong or prolonged stress can lead to cell death and inflammation of tissues. In this paper, we studied the role of the ER resident enzyme Fic in regulating the activation a specific stress response: the unfolded protein response. We found that animals lacking Fic regulation respond to simple stresses like constant light or fasting and feeding with amplified reactivity. Over time and repeated challenges, this results in these stressed cells and tissues becoming compromised.

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Why is it important?

In an animal, many tissues are needed to last a lifetime, so they must be resilient to repeated stresses and injuries. Since some tissues, like the pancreas, deal with frequent and repeated cellular stresses as part of their normal function, this “internal stress thermostat” controlled by Fic allows cells to customize their stress response to maximize both function and health of the tissue over a lifetime. Understanding how Fic is regulated and how this “stress thermostat” could be adjusted is an exciting future avenue of research. This is especially interesting in the context of diseases in which secretion stress plays a factor such as neurodegenerative disorders, diabetes, cancer, and other inflammatory diseases.

Read the Original

This page is a summary of: Fic-mediated AMPylation tempers the unfolded protein response during physiological stress, Proceedings of the National Academy of Sciences, August 2022, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2208317119.
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