論文 - 詳細
| RRC ID | 6439 |
|---|---|
| 著者 | Yang M, Sun J, Sun X, Shen Q, Gao Z, Yang C. |
| タイトル | Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis. |
| ジャーナル | PLoS Genet |
| Abstract |
Arginine methylation of histone and non-histone proteins is involved in transcription regulation and many other cellular processes. Nevertheless, whether such protein modification plays a regulatory role during apoptosis remains largely unknown. Here we report that the Caenorhabditis elegans homolog of mammalian type II arginine methyltransferase PRMT5 negatively regulates DNA damage-induced apoptosis. We show that inactivation of C. elegans prmt-5 leads to excessive apoptosis in germline following ionizing irradiation, which is due to a CEP-1/p53-dependent up-regulation of the cell death initiator EGL-1. Moreover, we provide evidence that CBP-1, the worm ortholog of human p300/CBP, functions as a cofactor of CEP-1. PRMT-5 forms a complex with both CEP-1 and CBP-1 and can methylate the latter. Importantly, down-regulation of cbp-1 significantly suppresses DNA damage-induced egl-1 expression and apoptosis in prmt-5 mutant worms. These findings suggest that PRMT-5 likely represses CEP-1 transcriptional activity through CBP-1, which represents a novel regulatory mechanism of p53-dependent apoptosis. |
| 巻・号 | 5(6) |
| ページ | e1000514 |
| 公開日 | 2009-6-1 |
| DOI | 10.1371/journal.pgen.1000514 |
| PMID | 19521535 |
| PMC | PMC2691592 |
| MeSH | Animals Apoptosis* / radiation effects Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / radiation effects Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA Damage* / radiation effects Down-Regulation* Histone Acetyltransferases / genetics Histone Acetyltransferases / metabolism Protein Binding Protein-Arginine N-Methyltransferases / genetics Protein-Arginine N-Methyltransferases / metabolism* Radiation, Ionizing Repressor Proteins / genetics Repressor Proteins / metabolism Transcription Factors / genetics Transcription Factors / metabolism Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism |
| IF | 5.175 |
| 引用数 | 42 |
| WOS 分野 | GENETICS & HEREDITY |
| リソース情報 | |
| 線虫 | tm536 |