Manzano, JasminArfat Kasu, YasarBrower, Christopher S.2021-03-192021-03-192021https://hdl.handle.net/11274/12828Creative Arts and Research SymposiumCreative Arts and Research SymposiumIntracellular protein aggregates associated with amyotrophic lateral sclerosis and other forms of neurodegeneration include fragments of the TAR DNA binding protein 43 (TDP43). Due to multiple cleavage sites within TDP43, a variety of protein fragments with different N-termini are produced during pathology. These fragments aggregate if not efficiently removed from cells. Previously, we reported that the aggregation of fragments bearing specific destabilizing N-terminal amino acids is prevented by their removal through the N-degron pathway of the ubiquitin proteasome system (UPS). However, it is unclear how fragments lacking destabilizing N-terminal amino are removed from cells. Here, we report that the chaperone BCL2-Associated Athanogene 6 (BAG6) interacts with aggregation-prone fragments, irrespective of their N-termini, and prevents their aggregation. We also found a separate E3-ubiquitin ligase of the UPS, RNF126, which may participate in the removal of TDP43 fragments. This work has identified novel players that help prevent protein aggregation associated with neurodegeneration.en-USPoster