論文 - 詳細
| RRC ID | 46550 |
|---|---|
| 著者 | Zhang T, Hwang HY, Hao H, Talbot C Jr, Wang J. |
| タイトル | Caenorhabditis elegans RNA-processing protein TDP-1 regulates protein homeostasis and life span. |
| ジャーナル | J Biol Chem |
| 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. |
| 巻・号 | 287(11) |
| ページ | 8371-82 |
| 公開日 | 2012-3-9 |
| DOI | 10.1074/jbc.M111.311977 |
| PII | S0021-9258(20)60983-8 |
| PMID | 22232551 |
| PMC | PMC3318719 |
| MeSH | Amyotrophic Lateral Sclerosis / genetics Amyotrophic Lateral Sclerosis / metabolism Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism DNA-Binding Proteins / biosynthesis* DNA-Binding Proteins / genetics Forkhead Transcription Factors Frontotemporal Lobar Degeneration / genetics Frontotemporal Lobar Degeneration / metabolism Genetic Complementation Test Homeostasis / physiology* Humans Longevity / physiology* Mutation Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 4.238 |
| 引用数 | 33 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm4439 |