論文 - 詳細
| RRC ID | 45758 |
|---|---|
| 著者 | Jiang HS, Wu YC. |
| タイトル | LIN-3/EGF promotes the programmed cell death of specific cells in Caenorhabditis elegans by transcriptional activation of the pro-apoptotic gene egl-1. |
| ジャーナル | PLoS Genet |
| Abstract |
Programmed cell death (PCD) is the physiological death of a cell mediated by an intracellular suicide program. Although key components of the PCD execution pathway have been identified, how PCD is regulated during development is poorly understood. Here, we report that the epidermal growth factor (EGF)-like ligand LIN-3 acts as an extrinsic signal to promote the death of specific cells in Caenorhabditis elegans. The loss of LIN-3 or its receptor, LET-23, reduced the death of these cells, while excess LIN-3 or LET-23 signaling resulted in an increase in cell deaths. Our molecular and genetic data support the model that the LIN-3 signal is transduced through LET-23 to activate the LET-60/RAS-MPK-1/ERK MAPK pathway and the downstream ETS domain-containing transcription factor LIN-1. LIN-1 binds to, and activates transcription of, the key pro-apoptotic gene egl-1, which leads to the death of specific cells. Our results provide the first evidence that EGF induces PCD at the whole organism level and reveal the molecular basis for the death-promoting function of LIN-3/EGF. In addition, the level of LIN-3/EGF signaling is important for the precise fine-tuning of the life-versus-death fate. Our data and the previous cell culture studies that say EGF triggers apoptosis in some cell lines suggest that the EGF-mediated modulation of PCD is likely conserved in C. elegans and humans. |
| 巻・号 | 10(8) |
| ページ | e1004513 |
| 公開日 | 2014-8-1 |
| DOI | 10.1371/journal.pgen.1004513 |
| PII | PGENETICS-D-13-02966 |
| PMID | 25144461 |
| PMC | PMC4140636 |
| MeSH | Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / biosynthesis* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Death / genetics* Cell Lineage / genetics Epidermal Growth Factor / genetics* Epidermal Growth Factor / metabolism ErbB Receptors / genetics ErbB Receptors / metabolism Gene Expression Regulation, Developmental Humans MAP Kinase Signaling System / genetics Repressor Proteins / biosynthesis* Repressor Proteins / genetics Transcription Factors / genetics Transcription Factors / metabolism Transcriptional Activation / genetics* |
| IF | 5.175 |
| 引用数 | 11 |
| 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 | X(Twitter) |
| 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 | tm1340 |