Abstract 1528 Role of Stv/BAG-3 in Protein Homeostasis

As we age, our cells begin to lose efficiency in their ability to degrade proteins, which are key to the cell's survival. We have previously found that the protein quality control gene starvin (stv) plays a role in age-dependent protein homeostasis by helping to target damaged/misfolded proteins for degradation. We also find that the p38 MAPK (p38Kb) is required for the localization of stv in the adult flight muscle z-disc and that p38Kb regulates stv mediated protein degradation. We also found that lamin is a target of p38Kb and stv for degradation. Our hypothesis is that p38Kb phosphorylates stv, which allows for the hand-off of lamin from stv to ref(2)p, an autolysosomal adapter protein. If this hand-off fails, the target protein will aggregate instead of being degraded. Therefore, we are testing if stv phosphorylation by p38Kb is important for this process. We have generated transgenic stv mutants that are phosphomimic or phosphonull at predicted p38Kb phosphorylation sites that are conserved between humans and Drosophila. We also generated a transgenic stv line in which the predicted p38Kb binding domain has been deleted. Our preliminary data suggest that manipulation of these sites can lead to new post-translational modifications (PTM) of stv and affect levels of lamin. Funding was from NIA and the Oregon State University Summer Undergraduate Research Experience.