論文 - 詳細
| RRC ID | 46427 |
|---|---|
| 著者 | Qi W, Huang X, Neumann-Haefelin E, Schulze E, Baumeister R. |
| タイトル | Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans. |
| ジャーナル | PLoS Genet |
| Abstract |
In Caenorhabditis elegans (C. elegans), the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR) signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension. In contrast to the cell-autonomous IIR signaling, which is required for larval germline proliferation, activation of DAF-16 in the hypodermis results in hyperplasia of the germline and disruption of the surrounding basement membrane. SHC-1 adaptor protein and AKT-1 kinase antagonize, whereas AKT-2 and SGK-1 kinases promote, this cell-nonautonomous DAF-16 function. Our data suggest that a functional balance of DAF-16 activities in different tissues determines longevity and reveals a novel, cell-nonautonomous role of FOXO/DAF-16 to affect stem cells. |
| 巻・号 | 8(8) |
| ページ | e1002836 |
| 公開日 | 2012-1-1 |
| DOI | 10.1371/journal.pgen.1002836 |
| PII | PGENETICS-D-12-00777 |
| PMID | 22916022 |
| PMC | PMC3420913 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Proliferation Cell Transformation, Neoplastic / genetics Cell Transformation, Neoplastic / metabolism* Forkhead Transcription Factors Gene Expression Regulation, Developmental Germ Cells / cytology Germ Cells / metabolism Humans Longevity / genetics* Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Proto-Oncogene Proteins c-akt / genetics Proto-Oncogene Proteins c-akt / metabolism Receptors, Somatomedin / genetics Receptors, Somatomedin / metabolism Shc Signaling Adaptor Proteins / genetics Shc Signaling Adaptor Proteins / metabolism Signal Transduction / genetics* Stem Cells / cytology Stem Cells / metabolism* Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 5.175 |
| 引用数 | 45 |
| WOS 分野 | GENETICS & HEREDITY |
| リソース情報 | |
| 線虫 | tm1729 |