Apoptosis and necroptosis regulate many aspects of organismal biology and are involved in various human diseases. TNF is well known to induce both of these forms of cell death and the underlying mechanisms have been elaborately described. However, cells can also engage apoptosis and necroptosis through TNF-independent mechanisms, involving, for example, activation of the pattern recognition receptors Toll-like receptor (TLR)-3 and -4, or zDNA-binding protein 1 (ZBP1). In this context, cell death signaling depends on the presence of receptor-interacting serine/threonine protein kinase 3 (RIPK3). Whereas RIPK3 is required for TNF-induced necroptosis, it mediates both apoptosis and necroptosis upon TLR3/4 and ZBP1 engagement. Here, we review the intricate mechanisms by which TNF-independent cell death is regulated by RIPK3.

中文翻译：

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不依赖于 TNF 的 RIPK3 介导的细胞死亡机制

细胞凋亡和坏死性凋亡调节有机体生物学的许多方面，并涉及多种人类疾病。众所周知，TNF 会诱导这两种形式的细胞死亡，并且已经详细描述了潜在的机制。然而，细胞也可以通过 TNF 独立机制参与细胞凋亡和坏死性凋亡，例如，涉及模式识别受体 Toll 样受体 (TLR)-3​​ 和 -4 或 zDNA 结合蛋白 1 (ZBP1) 的激活。在这种情况下，细胞死亡信号取决于受体相互作用的丝氨酸/苏氨酸蛋白激酶 3 (RIPK3) 的存在。尽管 RIPK3 是 TNF 诱导的坏死性凋亡所必需的，但它在 TLR3/4 和 ZBP1 结合后介导细胞凋亡和坏死性凋亡。在这里，我们回顾了 RIPK3 调节 TNF 非依赖性细胞死亡的复杂机制。