The avian virus-derived protein apoptin induces p53-independent apoptosis in a tumor-specific way. Apoptin acts as a multimeric complex and forms superstructures upon binding to DNA. In tumor cells, apoptin is phosphorylated and mainly nuclear, whereas in normal cells it is unphosphorylated, cytoplasmic, and becomes readily neutralized. Interestingly, apoptin phosphorylation, nuclear translocation, and apoptosis can transiently be induced in normal cells by cotransfecting SV40 large T oncogene, indicating that apoptin recognizes early stages of oncogenic transformation. In cancer cells, apoptin appears to recognize survival signals, which it is able to redirect into cell death impulses. Apoptin targets include DEDAF, Nur77, Nmi, Hippi, and the potential drug target APC1. Apoptin-transgenic mice and animal tumor models have revealed apoptin as a safe and efficient antitumor agent, resulting in significant tumor regression. Future antitumor therapies could use apoptin either as a therapeutic bullet or as an early sensor of druggable tumor-specific processes.

中文翻译：

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Apoptin：致癌转化早期传感器的治疗潜力。

禽病毒衍生蛋白凋亡素以肿瘤特异性方式诱导p53非依赖性凋亡。细胞凋亡蛋白充当多聚体复合物，并在与DNA结合后形成超结构。在肿瘤细胞中，凋亡素被磷酸化并且主要是核的，而在正常细胞中，其未磷酸化，细胞质的并且容易被中和。有趣的是，通过共转染SV40大T癌基因，可以在正常细胞中短暂诱导凋亡蛋白的磷酸化，核易位和凋亡，这表明凋亡蛋白可以识别致癌转化的早期阶段。在癌细胞中，凋亡素似乎可以识别生存信号，它能够重定向到细胞死亡的冲动中。Apoptin靶标包括DEDAF，Nur77，Nmi，Hippi和潜在的药物靶标APC1。Apoptin转基因小鼠和动物肿瘤模型显示Apoptin是一种安全有效的抗肿瘤剂，可导致明显的肿瘤消退。未来的抗肿瘤疗法可能将凋亡素用作治疗子弹或可药物治疗的肿瘤特异性过程的早期传感器。