EAGER: Elucidating the Mechanism of Pseudophosphatase MK-STYX as a Regulator of mRNA Stability in the Stress Response Pathway

College Of William And Mary, Williamsburg VA

Investigators

Abstract

When cells are exposed to stress such as high temperature or ultraviolet rays from the sun, they respond quickly to ensure survival. One of the most rapid responses is stopping protein production, which allows cells to adapt to stress. Cells maintain this control by sequestering messenger RNAs, which provide the blueprint for protein synthesis, to special compartments called stress granules. A messenger RNA binding protein named G3BP-1 is widely accepted as an important component of stress granules. Researchers recently reported that another protein called MK-STYX interacts with G3BP-1 and inhibits stress granule formation. Although stress granules have been studied extensively for the past eight years, most studies have focused exclusively on G3BP-1 and other components involved in regulating stress granule assembly. This research explores the novel role MK-STYX has in disassembly of stress granules and in blocking their formation. This study will provide insight into the role MK-STYX plays in the stress response, as a regulator of messenger RNA stability and in the dynamics of stress granule formation. The following specific aims will be addressed: (1) Determine the effect of MK-STYX on the cellular pathway responsible for protein production. Does MK-STYX indirectly activate or bypass this pathway to block stress granule assembly? Does MK-STYX stabilize protein production, which would prevent stress granule formation, or is it required for their disassembly? (2) Determine the effect of MK-STYX on the G3BP-1 complex required for stress granule assembly. Does MK-STYX disrupt interactions between G3BP-1 and other scaffold proteins, which are required for stress granule assembly? (3) Determine the effect of MK-STYX on the cell cytoskeleton and chaperones required for stress granule dynamics. Does MK-STYX interact with heat shock proteins required for disassembly, such as Hsp70? Broader Impacts. This project provides the opportunity to integrate seamlessly research and education. It will allow the investigator to enhance the biology curriculum at the College of William & Mary and to serve as a positive role model for underrepresented students. One of the investigator's goals is to design a lecture and laboratory course in biological chemistry, which will expose students to the study of protein-protein interactions and their function. Aims and results of her research will be incorporated into her teaching. The investigator has always been committed to programs that enhance participation of underrepresented groups in science. However, she has realized that just being a faculty member is not enough to retain African-Americans and other minorities in the sciences. It is imperative to encourage individuals from underrepresented groups to obtain PhDs become independent investigators themselves. The investigator will also participate in an HHMI-funded program that provides underrepresented groups with a unique undergraduate research experience and that and promotes collaborations with local historically black-serving institutions such as Hampton University, Norfolk State University, and Virginia State University to foster professional development and mentoring relationships between faculty and students. The investigator will continue to provide real research opportunities for her students so that they may engage in the exciting process of scientific discovery.