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Tatiana Prioleau

Class of 2022

Project Title: Is MK-STYX Reducing Stress Granules via the Autophagy Pathway?

Research Report

In today’s society, and particularly in William and Mary’s campus, the majority of people are stressed out, whether it is about school or their personal life. Like people, our cells can get “stressed out”. Exposing cells to ultraviolet light, heat, or harsh chemicals can initiation the cell’s stress response. A major way that cells respond to stressors is by forming membraneless droplets called stress granules. Stress granules are aggregations of messenger ribonucleic acid (mRNA) and protein. Stress granules “stay together” because of protein to protein interactions and mRNA cross-linkages. Stress granules are dynamic structures.  The mRNA and protein within them are moved around and modified and these contents can even be exchanged between granules . Stress granules serve as sites for mRNA storage and translation of proteins that are necessary for the stress response. They keep cells functioning under stressful conditions. Most importantly, stress granules are meant to be temporary structures in the cell. Once the stressor has ceased, the stress granules are then disassembled and cleared. If not cleared once the stress ceases, stress granules can become toxic to the cell and can affect major cellular processes. 

Research has shown that this particular protein mitogen activated protein kinase phosphoserine/threonine/tyrosine-binding protein (MK-STYX), reduces stress granules in cells. MK-STYX is a pseudophosphatase , meaning it is unable to remove phosphate groups from substrates. It was thought that MK-STYX was reducing stress granules because of its interaction with Ras-GTPase activation protein SH3 domain binding protein-1 (G3BP1), a nucleator and major protein found in stress granules cores (Hinton 2010). However, later research confirmed that MK-STYX is reducing stress granules independent of G3BP1 activation (Barr 2013). 

Research has also found that stress granules are reduced via autophagy. Autophagy (i.e self-eating) is a degradation pathway that encases damaged and defective macromolecules in vesicles to be broken down by enzymes in the lysosome. Since MK-STYX and autophagy both are involved in the reduction of stress granules in cells, I am trying to determine if MK-STYX is reducing stress granules via the autophagy pathway.