The N termini of tar DNA-binding protein 43 (TDP43) C-terminal fragments influence degradation, aggregation propensity, and morphology

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dc.contributor.authorKasu, Yasar Arfat T.
dc.contributor.authorAlemu, Samrawit
dc.contributor.authorLamari, Angela
dc.contributor.authorLoew, Nicole
dc.contributor.authorBrower, Christopher S.
dc.creator.orcidhttps://orcid.org/0000-0003-0289-5541
dc.date.accessioned2023-01-19T17:33:59Z
dc.date.available2023-01-19T17:33:59Z
dc.date.issued2018
dc.descriptionArticle originally published by Molecular and Cellular Biology, 38(19). English. Published online 2018. https://doi.org/10.1128/mcb.00243-18.
dc.description.abstractFragments 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 rule pathway, whereas degradation of TDP43219 continues in the absence of ATE1. These fragments also differ in their aggregation propensities and form morphologically distinct aggregates. This work reveals that the N termini of otherwise similar CTFs have profound effects on fragment behavior and may influence clinical outcomes in neurodegeneration associated with aggregation.en_US
dc.identifier.citationThis is the abstract for an article that is available at https://doi.org/10.1128/mcb.00243-18. Recommended citation: Kasu, Y. A., Alemu, S., Lamari, A., Loew, N., & Brower, C. S. (2018). The N termini of tar DNA-binding protein 43 (TDP43) C-terminal fragments influence degradation, aggregation propensity, and morphology. Molecular and Cellular Biology, 38(19). This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.en_US
dc.identifier.urihttps://hdl.handle.net/11274/14311
dc.identifier.urihttps://doi.org/10.1128/mcb.00243-18
dc.language.isoen_USen_US
dc.publisherTaylor and Francisen_US
dc.subjectTAR DNA-binding proteinen_US
dc.subjectAggregationen_US
dc.subjectAmyotrophic lateral sclerosisen_US
dc.subjectProteasomeen_US
dc.subjectAutophagyen_US
dc.titleThe N termini of tar DNA-binding protein 43 (TDP43) C-terminal fragments influence degradation, aggregation propensity, and morphologyen_US
dc.typeAbstracten_US

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