BmNPV p35 regulates apoptosis in Bombyx mori via a novel target of interaction with the BmVDAC2-BmRACK1 complex
文献类型： 外文期刊
第一作者： Zhu, Lin-Bao
作者： Zhu, Lin-Bao;Zhu, Han-Dan;Huang, Zhi-Hao;Cao, Hui-Hua;Ayaz, Sadaf;Yang, Jia-Yue;Chen, Xi-Ya;Zhang, Ying;Liu, Shi-Huo;Xu, Jia-Ping;Zhu, Lin-Bao;Zhu, Han-Dan;Huang, Zhi-Hao;Cao, Hui-Hua;Ayaz, Sadaf;Yang, Jia-Yue;Chen, Xi-Ya;Zhang, Ying;Liu, Shi-Huo;Xu, Jia-Ping;Zhu, Lin-Bao
作者机构：
关键词： BmVDAC2; BmRACK1; BmNPV; p35; Apoptosis
期刊名称：INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY （ 影响因子：3.8； 五年影响因子：4.4 ）
ISSN： 0965-1748
年卷期： 2024 年 169 卷
页码：
收录情况： SCI
摘要： Voltage -dependent anion channel 2 (VDAC2) is an important channel protein that plays a crucial role in the host response to viral infection. The receptor for activated C kinase 1 (RACK1) is also a key host factor involved in viral replication. Our previous research revealed that Bombyx mori VDAC2 (BmVDAC2) and B. mori RACK1 (BmRACK1) may interact with Bombyx mori nucleopolyhedrovirus (BmNPV), though the specific molecular mechanism remains unclear. In this study, the interaction between BmVDAC2 and BmRACK1 in the mitochondria was determined by various methods. We found that BmNPV p35 interacts directly with BmVDAC2 rather than BmRACK1. BmNPV infection significantly reduced the expression of BmVDAC2, and activated the mitochondrial apoptosis pathway. Overexpression of BmVDAC2 in BmN cells inhibited BmNPV-induced cytochrome c (cyto c) release, decrease in mitochondrial membrane potential as well as apoptosis. Additionally, the inhibition of cyto c release by BmVDAC2 requires the involvement of BmRACK1 and protein kinase C. Interestingly, overexpression of p35 inhibited cyto c release during mitochondrial apoptosis in a RACK1 and VDAC2dependent manner. Even the mutant p35, which loses Caspase inhibitory activity, could still bind to VDAC2 and inhibit cyto c release. In summary, our results indicated that BmNPV p35 interacts with the VDAC2-RACK1 complex to regulate apoptosis by inhibiting cyto c release. These findings confirm the interaction between BmVDAC2 and BmRACK1, the interaction between p35 and the VDAC2-RACK1 complex, and a novel target that BmNPV p35 regulates apoptosis in Bombyx mori via interaction with the BmVDAC2-BmRACK1 complex. The result provide an initial exploration of the function of this interaction in the BmNPV-induced mitochondrial apoptosis pathway.
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