The N Termini of TAR DNA-Binding Protein 43 (TDP43) C-Terminal Fragments Influence Degradation, Aggregation Propensity, and Morphology.

ABSTRACT: Fragments of the TAR DNA-binding protein 43 (TDP43) are major components of intracellular aggregates associated with amyotrophic lateral sclerosis and frontotemporal dementia. A variety of C-terminal fragments (CTFs) exist, with distinct N termini; however, little is known regarding their differences in metabolism and aggregation dynamics. Previously, we found that specific CTFs accumulate in the absence of the Arg/N-end rule pathway of the ubiquitin proteasome system (UPS) and that their degradation requires arginyl-tRNA protein transferase 1 (ATE1). Here, we examined two specific CTFs of TDP43 (TDP43²¹⁹ and TDP43²⁴⁷), which are ∼85% identical and differ at their N termini by 28 amino acids. We found that TDP43²⁴⁷ is degraded primarily by the Arg/N-end rul

SUBMITTER: Kasu YAT 

PROVIDER: S-EPMC6146831 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature