Research Symposium

BIO

My name is Karina Frey and I am a senior majoring in Cell and Molecular Neuroscience. I am originally from Tampa, Florida and have taken part of UROP for two years now as a student myself and a UROP leader. My research is concentrated in molecular biology looking at different cellular pathways that mediate with toxic/misfolded protein degradation. I have enjoyed every moment of the research process and have gained a lot of wisdom from my research mentor. Beyond research, I also am part of a medical fraternity, Phi Delta Epsilon, Dance Marathon and am on Level Dance Company's team! I look forward to the future in pursuing a career in medicine as I am on the pre-med track and hope to apply to medical school!

The role of SUMOylation in Cdc48 mediated stress granule clearance

Abstract

SUMO (small ubiquitin-like modifier) is a protein that can be added to substrate proteins in a process called SUMOylation, which is a cellular post translational modification. SUMOylation functions in protein translocation, DNA replication, stress response, and protein degradation. Stress granules (SGs) are condensates of mRNA and misfolded proteins that form during stress. This promotes cell survival by sequestering inactive mRNAs and toxic misfolded proteins from the cellular environment until the stress is resolved. Stress granules are cleared by various mechanisms, but we focus on Cdc48 complex mediated clearance. The Cdc48 complex is an ATPase that serves as a segregase/unfoldase that can unfold misfolded proteins before targeting them to the proteasome. The Cdc48 complex consists of three subunits: the Cdc48 core particle, Ufd1, and Npl4. While Npl4 contains a ubiquitin interacting motif, Ufd1 contains a SUMO interacting motif (SIM). This allows for the recognition of SUMOylated substrates. The protein components of SGs can be SUMOylated and ubiquitinated, which aids in their clearance. However, the role of SUMOylation in Cdc48-mediated clearance is unknown. My research lab evaluates the relationship between SUMOylation, ubiquitination, and the cytotoxic stress response in an S. cerevisiae yeast model. After being exposed to stress, such as treatment with arsenite or heat shock, we observed how the Cdc48-mediated clearance was affected in various SUMOylation and ubiquitination mutants. We found that SG clearance was negatively affected in mutants where SUMOylation and ubiquitination were impaired. In addition, we found that SG clearance was impaired in Cdc48 complex mutants.

Keywords: SUMOylation, Cdc48 complex, stress granule clearance