Master of Science (M.Sc.)
Shanta D Hinton
John C Poutsma
The cell imposes order upon its otherwise chaotic milieu of biomolecules via a series of delineated regions, deemed organelles, by means of encapsulating functionally related proteins within a membrane. Alternatively, however, cells can introduce transient, local increases in order via the inducement of phase separated “membrane-less” organelles. One type of biomolecular condensate is the stress granule (SG), which is a dynamic cytosolic granule formed in response to a myriad of cellular stressors. Recently, MK-STYX has been demonstrated to decrease the number of SGs within HEK293 cells in response to arsenite treatment, indicating a regulatory role within this stress response pathway. Interestingly, a series of seemingly unrelated observations pertaining to MK-STYX have converged on a shared mechanism of regulatory action, centered around SG formation and dispersal. Specifically, MK-STYX is demonstrated in the following work to utilize its DUSP domain to negatively regulate the phosphorylation status of a critical tyrosine residue in G3BP1 (a SG nucleator) as a means of impeding SG formation. Additionally, through low-affinity interactions with β-II spectrin (a cytoskeletal protein), MK-STYX may influence the translocation of these transient condensates to their autophagic destruction. The following work thus highlights the integral role MK-STYX plays in the life cycle of SGs, and further demonstrates the functional utility of a seemingly innocuous pseudophosphatase.
© The Author
Smailys, Jonathan, "Exploring The Role Of Mk-Styx In The Cellular Stress Response" (2023). Dissertations, Theses, and Masters Projects. William & Mary. Paper 1697552699.