Cysteine protease cathepsin B mediates radiation-induced bystander effects.
Cysteine protease cathepsin B mediates radiation-induced bystander effects.
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DOI：
10.1038/nature23284
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发表时间：
2017-07-27
期刊：
影响因子：
64.8
通讯作者：
Xue D
中科院分区：
文献类型：
--
作者：
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
辐射诱导的旁观者效应（RIBE）是指受辐射细胞或组织释放的因子对动物未暴露于辐射的其他部位产生影响，导致基因组不稳定、应激反应和细胞凋亡或细胞增殖改变的一种独特过程。尽管RIBE因子在放射防护、放射安全和放射治疗中具有重要意义，但其分子特性及其作用机制仍不明确。本研究以秀丽隐杆线虫为动物模型研究RIBE，并鉴定出一种与人组织蛋白酶B同源的半胱氨酸蛋白酶pr -4作为线虫中的第一个RIBE因子。CPR-4是由受紫外线（UV）或电离伽马射线（IR）照射的动物分泌的，是条件培养基中导致抑制细胞死亡和增加未受照射动物胚胎死亡率的主要因素。此外，CPR-4在辐照组织远端未暴露部位引起这些影响和应激反应。在对辐射的反应中，pr -4的活性受p53同源物cep1的调控，并且似乎通过胰岛素样生长因子受体DAF-2发挥RIBE的作用。我们的研究为难以捉摸的RIBE提供了关键的见解，并将有助于识别其他RIBE因子及其作用机制。
Radiation-induced bystander effects (RIBE) refer 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. Despite important implications in radioprotection, radiation safety and radiotherapy, the molecular identities of RIBE factors and their mechanisms of action remain elusive. Here we use C. elegans as an animal model to study RIBE and have identified a cysteine protease CPR-4, a human cathepsin B homolog, as the first RIBE factor in nematodes. CPR-4 is secreted from animals irradiated with ultraviolet (UV) or ionizing gamma rays (IR) and is the major factor in the conditioned medium that leads to inhibition of cell death and increased embryonic lethality in unirradiated animals. Moreover, CPR-4 causes these effects and stress response at unexposed sites distal to the irradiated tissue. The activity of CPR-4 is regulated by the p53 homolog cep-1 in response to radiation and CPR-4 appears to act through the insulin-like growth factor receptor, DAF-2, to exert RIBE. Our study provides critical insights into the elusive RIBE and will facilitate identification of additional RIBE factors and their mechanisms of action.
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影响因子：
3.4
作者：
Chang, CC;Sun, W;Trosko, JE
通讯作者：
Trosko, JE
影响因子：
64.8
作者：
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3.1
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Johnstone, IL
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2.8
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Khvostunov, IK
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作者：
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通讯作者：
Boothman, D. A.