Cysteine protease cathepsin B mediates radiationinduced bystander effects

Yu Peng, Man Zhang, Lingjun Zheng, Qian Liang, Hanzeng Li, Jeng Ting Chen, Hongyan Guo, Sawako Yoshina, Yu Zen Chen, Xiang Zhao, Xiaoqi Wu, Bin Liu, Shohei Mitani, Jau Song Yu, Ding Xue

Research output: Contribution to journalJournal Article peer-review

58 Scopus citations

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.

Original languageEnglish
Pages (from-to)458-462
Number of pages5
JournalNature
Volume547
Issue number7664
DOIs
StatePublished - 27 07 2017

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© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

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