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• W2024858047 endingPage "8382" @default.
• W2024858047 startingPage "8371" @default.
• W2024858047 abstract "Transactive response DNA-binding protein (TARDBP/TDP-43), a heterogeneous nuclear ribonucleoprotein (hnRNP) with diverse activities, is a common denominator in several neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Orthologs of TDP-43 exist in animals ranging from mammals to invertebrates. Here, we systematically studied mutant Caenorhabditis elegans lacking the nematode TDP-43 ortholog, TDP-1. Heterologous expression of human TDP-43 rescued the defects in C. elegans lacking TDP-1, suggesting their functions are conserved. Although the tdp-1 mutants exhibited deficits in fertility, growth, and locomotion, loss of tdp-1 attenuated defects in several C. elegans models of proteotoxicity. Loss of tdp-1 suppressed defects in transgenic C. elegans expressing TDP-43 or CuZn superoxide dismutase, both of which are associated with proteotoxicity in neurodegenerative diseases. Loss of tdp-1 also reduced defects in mutant animals lacking the heat shock factor HSF-1. Transcriptional profiling demonstrated that the loss of TDP-1 altered expression of genes functioning in RNA processing and protein folding. Furthermore, the absence of tdp-1 extended the life span in C. elegans. The life span extension required a FOXO transcriptional factor DAF-16 but not HSF-1. These results suggest that the C. elegans TDP-1 has a role in the regulation of protein homeostasis and aging." @default.
• W2024858047 created "2016-06-24" @default.
• W2024858047 creator A5009065583 @default.
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• W2024858047 creator A5051197797 @default.
• W2024858047 creator A5081445006 @default.
• W2024858047 creator A5085969813 @default.
• W2024858047 date "2012-03-01" @default.
• W2024858047 modified "2023-10-14" @default.
• W2024858047 title "Caenorhabditis elegans RNA-processing Protein TDP-1 Regulates Protein Homeostasis and Life Span" @default.
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• W2024858047 doi "https://doi.org/10.1074/jbc.m111.311977" @default.
• W2024858047 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3318719" @default.
• W2024858047 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22232551" @default.
• W2024858047 hasPublicationYear "2012" @default.
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