Pinellia pedatisecta agglutinin (PPA) is a specific mannose-binding plant lectin accumulated in the tuber of P. pedatisecta. In the work presented, the cytotoxicity of PPA to cancer cells was investigated through exogenous expression. A PPA gene was transduced into normal and cancer cell lines through plasmid vectors, and the effect of PPA expression was examined. Results showed that PPA translocated into the nucleus, colocalized with DNA and induced cell death. A mannose-binding motif and a V(103)-W(130) region directed the nuclear translocation of PPA. Coprecipitation, mass spectrometry and western blotting analysis further indentified that PPA was associated with the methylosome, which contains methylosome protein 50 and protein arginine methyltransferase 5 (PRMT5). Knockdown of PRMT5 significantly inhibited the PPA-induced cell death, suggesting that PPA used the methylosome as a target. Furthermore, Ad.surp-PPA, an adenovirus vector in which the PPA gene was controlled by a survivin promoter (surp), selectively inhibited the proliferation of cancer cell lines. Taken together, the expression of PPA gene elicited significant cytotoxicity to cancer cells through targeting the methylosome and might be developed into a novel agent in cancer gene therapy.

中文翻译：

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半夏凝集素与甲基化体相互作用并诱导癌细胞死亡。

半夏凝集素 (PPA) 是一种特定的甘露糖结合植物凝集素，积聚在半夏的块茎中。在介绍的工作中，通过外源表达研究了 PPA 对癌细胞的细胞毒性。通过质粒载体将PPA基因转导到正常细胞系和癌细胞系中，并检测PPA表达的影响。结果表明，PPA 易位到细胞核中，与 DNA 共定位并诱导细胞死亡。甘露糖结合基序和 V(103)-W(130) 区域指导 PPA 的核易位。共沉淀、质谱和蛋白质印迹分析进一步确定 PPA 与甲基小体相关，其中包含甲基小体蛋白 50 和蛋白精氨酸甲基转移酶 5 (PRMT5)。PRMT5 的敲低显着抑制了 PPA 诱导的细胞死亡，表明 PPA 使用甲基化体作为目标。此外，Ad.surp-PPA 是一种腺病毒载体，其中 PPA 基因受存活蛋白启动子 (surp) 控制，选择性抑制癌细胞系的增殖。总之，PPA基因的表达通过靶向甲基化体对癌细胞产生显着的细胞毒性，并可能被开发成癌症基因治疗的新药物。