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Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy.
Cytokine & Growth Factor Reviews ( IF 13.0 ) Pub Date : 2003-06-06 , DOI: 10.1016/s1359-6101(03)00029-7
Alexandru Almasan 1 , Avi Ashkenazi
Affiliation  

Apo2 ligand or tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL) is one of several members of the TNF gene superfamily that induce apoptosis through engagement of death receptors. Apo2L/TRAIL is unusual as compared to any other cytokine as it interacts with a complex system of receptors: two pro-apoptotic death receptors and three anti-apoptotic decoys. This protein has generated tremendous excitement as a potential tumor-specific cancer therapeutic because, as a stable soluble trimer, it selectively induces apoptosis in many transformed cells but not in normal cells. Transcriptional activation of Apo2L/TRAIL by interferons (IFNs) through specific regulatory elements in its promoter, and possibly by a number of other cytokines, reveals its possible involvement in the activation of natural killer cells, cytotoxic T lymphocytes, and dendritic cells. In this review, we focus on the apoptosis signaling pathways stimulated by Apo2L/TRAIL, summarize what is known to date about the physiological role of this ligand and the potential for its application to cancer therapy.

中文翻译:

Apo2L / TRAIL:细胞凋亡信号传导,生物学和癌症治疗潜力。

Apo2配体或与肿瘤坏死因子(TNF)相关的凋亡诱导配体(Apo2L / TRAIL)是TNF基因超家族的几个成员之一,该成员通过死亡受体的结合而诱导凋亡。与任何其他细胞因子相比,Apo2L / TRAIL与其他任何细胞因子相比都是不同寻常的,因为它与复杂的受体系统相互作用:两个促凋亡死亡受体和三个抗凋亡诱饵。这种蛋白质作为一种潜在的肿瘤特异性癌症治疗剂引起了极大的兴奋,因为作为一种稳定的可溶性三聚体,它选择性地诱导了许多转化细胞的凋亡,而没有诱导正常细胞的凋亡。干扰素(IFN)通过其启动子中的特定调控元件(可能还有许多其他细胞因子)对Apo2L / TRAIL的转录激活,表明其可能参与了自然杀伤细胞的激活,细胞毒性T淋巴细胞和树突状细胞。在这篇综述中,我们着重于Apo2L / TRAIL刺激的细胞凋亡信号通路,总结了迄今为止已知的关于该配体的生理作用及其在癌症治疗中的应用潜力。
更新日期:2019-11-01
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