論文 - 詳細
| RRC ID | 3630 |
|---|---|
| 著者 | Schertel C, Conradt B. |
| タイトル | C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions. |
| ジャーナル | Development |
| Abstract |
To obtain insight into the role of the retinoblastoma susceptibility gene (Rb; also known as Rb1) in apoptosis, we analyzed Caenorhabditis elegans mutants lacking a functional lin-35 RB gene. We found that the loss of lin-35 function results in a decrease in constitutive germ cell apoptosis. We present evidence that lin-35 promotes germ cell apoptosis by repressing the expression of ced-9, an anti-apoptotic C. elegans gene that is orthologous to the human proto-oncogene BCL2. Furthermore, we show that the genes dpl-1 DP, efl-1 E2F and efl-2 E2F also promote constitutive germ cell apoptosis. However, in contrast to lin-35, dpl-1 (and probably also efl-1 and efl-2) promotes germ cell apoptosis by inducing the expression of the pro-apoptotic genes ced-4 and ced-3, which encode an APAF1-like adaptor protein and a pro-caspase, respectively. Based on these results, we propose that C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions in the germ line and that the transcriptional regulation of components of the central apoptosis machinery is a critical determinant of constitutive germ cell apoptosis in C. elegans. Finally, we demonstrate that lin-35, dpl-1 and efl-2, but not efl-1, function either downstream of or in parallel to cep-1 p53 (also known as TP53) and egl-1 BH3-only to cause DNA damage-induced germ cell apoptosis. Our results have implications for the general mechanisms through which RB-like proteins control gene expression, the role of RB-, DP- and E2F-like proteins in apoptosis, and the regulation of apoptosis. |
| 巻・号 | 134(20) |
| ページ | 3691-701 |
| 公開日 | 2007-10-1 |
| DOI | 10.1242/dev.004606 |
| PII | dev.004606 |
| PMID | 17881492 |
| MeSH | Animals Animals, Genetically Modified Apoptosis / physiology* Caenorhabditis elegans / anatomy & histology Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism DNA Damage E2F Transcription Factors / genetics E2F Transcription Factors / metabolism Germ Cells / cytology Germ Cells / physiology* Humans Protein Isoforms / genetics Protein Isoforms / metabolism* Proto-Oncogene Mas Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism RNA Interference RNA, Messenger / metabolism Retinoblastoma Protein / genetics Retinoblastoma Protein / metabolism* Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 5.611 |
| 引用数 | 46 |
| WOS 分野 | DEVELOPMENTAL 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 | F1000Research |
| 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 | tm2359 |