論文 - 詳細
| RRC ID | 46333 |
|---|---|
| 著者 | Rutkowski R, Dickinson R, Stewart G, Craig A, Schimpl M, Keyse SM, Gartner A. |
| タイトル | Regulation of Caenorhabditis elegans p53/CEP-1-dependent germ cell apoptosis by Ras/MAPK signaling. |
| ジャーナル | PLoS Genet |
| Abstract |
Maintaining genome stability in the germline is thought to be an evolutionarily ancient role of the p53 family. The sole Caenorhabditis elegans p53 family member CEP-1 is required for apoptosis induction in meiotic, late-stage pachytene germ cells in response to DNA damage and meiotic recombination failure. In an unbiased genetic screen for negative regulators of CEP-1, we found that increased activation of the C. elegans ERK orthologue MPK-1, resulting from either loss of the lip-1 phosphatase or activation of let-60 Ras, results in enhanced cep-1-dependent DNA damage induced apoptosis. We further show that MPK-1 is required for DNA damage-induced germ cell apoptosis. We provide evidence that MPK-1 signaling regulates the apoptotic competency of germ cells by restricting CEP-1 protein expression to cells in late pachytene. Restricting CEP-1 expression to cells in late pachytene is thought to ensure that apoptosis doesn't occur in earlier-stage cells where meiotic recombination occurs. MPK-1 signaling regulates CEP-1 expression in part by regulating the levels of GLD-1, a translational repressor of CEP-1, but also via a GLD-1-independent mechanism. In addition, we show that MPK-1 is phosphorylated and activated upon ionising radiation (IR) in late pachytene germ cells and that MPK-1-dependent CEP-1 activation may be in part direct, as these two proteins interact in a yeast two-hybrid assay. In summary, we report our novel finding that MAP kinase signaling controls CEP-1-dependent apoptosis by several different pathways that converge on CEP-1. Since apoptosis is also restricted to pachytene stage cells in mammalian germlines, analogous mechanisms regulating p53 family members are likely to be conserved throughout evolution. |
| 巻・号 | 7(8) |
| ページ | e1002238 |
| 公開日 | 2011-8-1 |
| DOI | 10.1371/journal.pgen.1002238 |
| PII | PGENETICS-D-11-00390 |
| PMID | 21901106 |
| PMC | PMC3161941 |
| MeSH | Animals Apoptosis* Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* DNA Damage Gene Expression Regulation, Developmental Genes, p53 Germ Cells / cytology Germ Cells / metabolism MAP Kinase Signaling System Meiosis Mitogen-Activated Protein Kinase 1 / genetics Mitogen-Activated Protein Kinase 1 / metabolism* Pachytene Stage / genetics Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism* Signal Transduction Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* Two-Hybrid System Techniques ras Proteins / genetics ras Proteins / metabolism* |
| IF | 5.175 |
| 引用数 | 43 |
| WOS 分野 | GENETICS & HEREDITY |
| 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 | |
| 各媒体での言及数の合計 | 1 |
| 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 | tm853 |