Recently we have found that cytokine IL-2 and innate immunity protein Tag7 activate cytotoxic lymphocytes that kill HLA-negative tumor cells, inducing both apoptosis and necroptosis. Here we decrypt the processes, taking part in necroptosis execution after FasL-Fas interaction. Necroptosis begins with RIPK1 activation and necrosome formation. Subsequent activation of MLKL results in the increase of Ca2+ level in the cell and activation of Ca2+-dependent enzymes causing lysosomal membrane permeabilization and the release of cathepsins to the cytosol. STAT3 translocation to the mitochondria and binding to a component of the respiratory chain complex I causes ROS accumulation. We have shown that transduction of necroptotic signal via TNFR1 and Fas has many common points. It is known that apoptosis plays a major role in physiological cell death; however, under pathological conditions necroptosis is very common. That is why the detailed mechanisms of FasL-Fas necroptosis can help in understanding the processes of elimination of tumor cells that have blocked apoptosis signal transduction.

最近，我们发现细胞因子IL-2和先天免疫蛋白Tag7激活杀死HLA阴性肿瘤细胞的细胞毒性淋巴细胞，从而诱导凋亡和坏死性坏死。在这里，我们对过程进行解密，并在FasL-Fas交互作用后参与坏死病的执行。坏死病始于RIPK1激活和坏死体形成。MLKL的后续激活导致细胞中Ca2 +水平的增加和Ca2 +依赖性酶的激活，导致溶酶体膜通透化和组织蛋白酶向细胞质的释放。STAT3易位至线粒体并与呼吸链复合体I的成分结合会导致ROS积累。我们已经表明，通过TNFR1和Fas传导坏死性信号具有许多共同点。已知细胞凋亡在生理细胞死亡中起主要作用。但是，在病理条件下，尸检是非常常见的。这就是为什么FasL-Fas坏死病的详细机制可以帮助理解消除阻断细胞凋亡信号转导的肿瘤细胞的过程的原因。