論文 - 詳細
| RRC ID | 35720 |
|---|---|
| 著者 | Khoshnood B, Dacklin I, Grabbe C. |
| タイトル | Urm1: an essential regulator of JNK signaling and oxidative stress in Drosophila melanogaster. |
| ジャーナル | Cell Mol Life Sci |
| Abstract |
Ubiquitin-related modifier 1 (Urm1) is a ubiquitin-like molecule (UBL) with the dual capacity to act both as a sulphur carrier and posttranslational protein modifier. Here we characterize the Drosophila melanogaster homologues of Urm1 (CG33276) and its E1 activating enzyme Uba4 (CG13090), and show that they function together to induce protein urmylation in vivo. Urm1 conjugation to target proteins in general, and to the evolutionary conserved substrate Peroxiredoxin 5 (Prx5) specifically, is dependent on Uba4. A complete loss of Urm1 is lethal in flies, although a small number of adult zygotic Urm1 (n123) mutant escapers can be recovered. These escapers display a decreased general fitness and shortened lifespan, but in contrast to their S. cerevisiae counterparts, they are resistant to oxidative stress. Providing a molecular explanation, we demonstrate that cytoprotective JNK signaling is increased in Urm1 deficient animals. In agreement, molecular and genetic evidence suggest that elevated activity of the JNK downstream target genes Jafrac1 and gstD1 strongly contributes to the tolerance against oxidative stress displayed by Urm1 (n123) null mutants. In conclusion, Urm1 is a UBL that is involved in the regulation of JNK signaling and the response against oxidative stress in the fruit fly. |
| 巻・号 | 73(9) |
| ページ | 1939-54 |
| 公開日 | 2016-5-1 |
| DOI | 10.1007/s00018-015-2121-x |
| PII | 10.1007/s00018-015-2121-x |
| PMID | 26715182 |
| MeSH | Amino Acid Sequence Animals Animals, Genetically Modified / metabolism Drosophila Proteins / classification Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / drug effects Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism* JNK Mitogen-Activated Protein Kinases / metabolism* Larva / metabolism Longevity MAP Kinase Signaling System Molecular Sequence Data Mutagenesis Nucleotidyltransferases / classification Nucleotidyltransferases / metabolism Oxidative Stress Paraquat / toxicity Peroxidases / genetics Peroxidases / metabolism Phylogeny Sequence Alignment Ubiquitin / classification Ubiquitin / genetics Ubiquitin / metabolism* |
| IF | 6.496 |
| 引用数 | 12 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL 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 | 3 |
| 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 | |
| ショウジョウバエ | 13090R-1 13090R-2 |