Yoshina Sawako
   Department   School of Medicine, School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Cysteine protease cathepsin B mediates radiation-induced bystander effects.
Journal Formal name:Nature
Abbreviation:Nature
ISSN code:(1476-4687)0028-0836(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 547(7664),pp.458-462
Author and coauthor Peng Yu, Zhang Man, Zheng Lingjun, Liang Qian, Li Hanzeng, Chen Jeng-Ting, Guo Hongyan, Yoshina Sawako, Chen Yu-Zen, Zhao Xiang, Wu Xiaoqi, Liu Bin, Mitani Shohei, Yu Jau-Song, Xue Ding
Publication date 2017/07
Summary 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.
DOI 10.1038/nature23284
PMID 28723894