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.