The Brower Lab
at Texas Woman's University
artwork by E. Brower
BAG6 prevents the aggregation of neurodegeneration-associated fragments of TDP43.
iScience (2022)
Yasar Arfat T. Kasu, Akshaya Arva, Jess Johnson, Christin Sajan, Jasmin Manzano, Andrew Hennes, Jacy Haynes, and Christopher S. Brower.
This study shows that BAG6 acts as a sensor for such hydrophobic fragments, including disease-associated TDP43 C-terminal fragments, and prevents their aggregation by promoting ubiquitylation through RNF126. The findings suggest that BAG6 has a broader role in protecting against neurodegeneration by solubilizing multiple aggregation-prone proteolytic fragments.
The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6
Proceedings of the National Academy of Sciences (2021)
Akshaya Arva, Yasar Arfat T Kasu, Jennifer Duncan, Mosleh A Alkhatatbeh, Christopher S Brower.
This study shows that Liat1, a protein of unknown function that interacts with Ate1, contains an intrinsically disordered region (IDR) that drives its nucleolar localization through liquid-liquid phase separation (LLPS). The nucleolar targeting depends on a low-complexity poly-lysine (poly-K) motif within the IDR. The study also shows that Jmjd6 modifies Liat1 in a poly-K–dependent manner, inhibiting its nucleolar localization and potentially regulating its LLPS-related functions.
Texas Journal of Microscopy (2020)
Yasar Arfat T. Kasu, Rinki Dasgupta, Christopher S Brower
Aging (2019)
Olga I Kechko, Irina Yu Petrushanko, Christopher S Brower, Alexei A Adzhubei, Alexey A Moskalev
Molecular and Cellular Biology (2018)
Yasar AT Kasu, Samrawit Alemu, Angela Lamari, Nicole Loew, Christopher S Brower
This study shows that TDP43 fragments with nearly identical sequences can differ significantly in how they are degraded and how they aggregate. Small differences at the N terminus determine whether a fragment depends on the Arg/N-end rule pathway for degradation. These differences also influence the appearance and behavior of aggregates, suggesting that subtle sequence variation may impact disease progression in neurodegeneration.