| RRC ID |
51442
|
| 著者 |
Peng Y, Zhang M, Zheng L, Liang Q, Li H, Chen JT, Guo H, Yoshina S, Chen YZ, Zhao X, Wu X, Liu B, Mitani S, Yu JS, Xue D.
|
| タイトル |
Cysteine protease cathepsin B mediates radiation-induced bystander effects.
|
| ジャーナル |
Nature
|
| Abstract |
The radiation-induced bystander effect (RIBE) refers to a unique process in which factors released by irradiated cells or tissues exert effects on other parts of the animal not exposed to radiation, causing genomic instability, stress responses and altered apoptosis or cell proliferation. Although RIBEs have important implications for radioprotection, radiation safety and radiotherapy, the molecular identities of RIBE factors and their mechanisms of action remain poorly understood. Here we use Caenorhabditis elegans as a model in which to study RIBEs, and identify the cysteine protease CPR-4, a homologue of human cathepsin B, as the first RIBE factor in nematodes, to our knowledge. CPR-4 is secreted from animals irradiated with ultraviolet or ionizing gamma rays, and is the major factor in the conditioned medium that leads to the inhibition of cell death and increased embryonic lethality in unirradiated animals. Moreover, CPR-4 causes these effects and stress responses at unexposed sites distal to the irradiated tissue. The activity of CPR-4 is regulated by the p53 homologue CEP-1 in response to radiation, and CPR-4 seems to exert RIBEs by acting through the insulin-like growth factor receptor DAF-2. Our study provides crucial insights into RIBEs, and will facilitate the identification of additional RIBE factors and their mechanisms of action.
|
| 巻・号 |
547(7664)
|
| ページ |
458-462
|
| 公開日 |
2017-7-27
|
| DOI |
10.1038/nature23284
|
| PII |
nature23284
|
| PMID |
28723894
|
| PMC |
PMC5892829
|
| MeSH |
Animals
Bystander Effect / radiation effects*
Caenorhabditis elegans / cytology
Caenorhabditis elegans / enzymology*
Caenorhabditis elegans / radiation effects*
Caenorhabditis elegans Proteins / metabolism
Cathepsin B / metabolism*
Cysteine Proteases / metabolism
Receptor, Insulin / metabolism
Ultraviolet Rays
|
| IF |
42.779
|
| 引用数 |
25
|
| リソース情報 |
| 線虫 |
tm3718 |
