BAG6 prevents the aggregation of neurodegeneration-associated fragments of TDP43

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dc.contributor.authorKasu, Yasar Arfat T.
dc.contributor.authorArva, Akshaya
dc.contributor.authorSajan, Christin
dc.contributor.authorManzano, Jasmin
dc.contributor.authorHennes, Andrew
dc.contributor.authorHaynes, Jacy
dc.contributor.authorBrower, Christopher S.
dc.creator.orcidhttps://orcid.org/0000-0003-0289-5541
dc.date.accessioned2023-01-18T17:37:40Z
dc.date.available2023-01-18T17:37:40Z
dc.date.issued2022
dc.descriptionArticle originally published by IScience, 25(5). English. Published online 2022. https://doi.org/10.1016/j.isci.2022.104273.
dc.description.abstractNeurodegeneration is associated with the aggregation of proteins bearing solvent-exposed hydrophobicity as a result of their misfolding and/or proteolytic cleavage. An understanding of the cellular protein quality control mechanisms which prevent protein aggregation is fundamental to understanding the etiology of neurodegeneration. By examining the metabolism of disease-linked C-terminal fragments of the TAR DNA-binding protein 43 (TDP43), we found that the Bcl-2 associated athanogene 6 (BAG6) functions as a sensor of proteolytic fragments bearing exposed hydrophobicity and prevents their intracellular aggregation. In addition, BAG6 facilitates the ubiquitylation of TDP43 fragments by recruiting the Ub-ligase, Ring finger protein 126 (RNF126). Authenticating its role in preventing aggregation, we found that TDP43 fragments form intracellular aggregates in the absence of BAG6. Finally, we found that BAG6 could interact with and solubilize additional neurodegeneration-associated proteolytic fragments. Therefore, BAG6 plays a general role in preventing intracellular aggregation associated with neurodegeneration.en_US
dc.identifier.citationThis is the published version of an article that is available at https://doi.org/10.1016/j.isci.2022.104273. Recommended citation: Kasu, Y. A., Arva, A., Johnson, J., Sajan, C., Manzano, J., Hennes, A., Haynes, J., & Brower, C. S. (2022). Bag6 prevents the aggregation of neurodegeneration-associated fragments of TDP43. IScience, 25(5), 104273. 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/11274/14309
dc.identifier.urihttps://doi.org/10.1016/j.isci.2022.104273
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.rights.licenseCC-BY 4.0
dc.subjectProteolytic cleavageen_US
dc.subjectIntracellular aggregationen_US
dc.subjectHydrophobicityen_US
dc.titleBAG6 prevents the aggregation of neurodegeneration-associated fragments of TDP43en_US
dc.typeArticleen_US

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