Translational Inflammation Research, Medical Faculty, Otto von Guericke University Magdeburg, 39106 Magdeburg, Germany.
Cells. 2024 Nov 3;13(21):1814. doi: 10.3390/cells13211814.
The mechanisms of CD95 (Fas/APO-1)-mediated extrinsic apoptotic pathway in cancer cells have been extensively studied. The majority of human cells express CD95, but not all these cells can induce extrinsic apoptosis. Accumulating evidence has shown that CD95 is a multifunctional protein, and its stimulation can also elicit non-apoptotic or even survival signals. It has become clear that under certain cellular contexts, due to the various checkpoints, CD95 activation can trigger both apoptotic and non-apoptotic signals. The crosstalk of death and survival signals may occur at different levels of signal transduction. The strength of the CD95 stimulation, initial levels of anti-apoptotic proteins, and posttranslational modifications of the core DISC components have been proposed to be the most important factors in the life/death decisions at CD95. Successful therapeutic targeting of CD95 signaling pathways will require a better understanding of the crosstalk between CD95-induced apoptotic and cell survival pathways. In this review, in order to gain a systematic understanding of the crosstalk between CD95-mediated apoptosis and non-apoptotic signaling, we will discuss these issues in a step-by-step way.
CD95（Fas/APO-1）介导的细胞外在凋亡途径的机制已被广泛研究。大多数人类细胞表达 CD95，但并非所有这些细胞都能诱导外在凋亡。越来越多的证据表明，CD95 是一种多功能蛋白，其刺激也可以引发非凋亡甚至存活信号。很明显，在某些细胞环境下，由于存在各种检查点，CD95 的激活可以触发凋亡和非凋亡信号。死亡和存活信号的串扰可能发生在信号转导的不同水平。CD95 刺激的强度、抗凋亡蛋白的初始水平以及核心 DISC 成分的翻译后修饰已被提出是 CD95 生死决策的最重要因素。成功的 CD95 信号通路治疗靶向需要更好地理解 CD95 诱导的凋亡和细胞存活途径之间的串扰。在这篇综述中，为了系统地理解 CD95 介导的凋亡与非凋亡信号之间的串扰，我们将逐步讨论这些问题。
