Necroptosis-independent signaling by the RIP kinases in inflammation.
Necroptosis-independent signaling by the RIP kinases in inflammation.
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DOI：
10.1007/s00018-016-2203-4
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Chan FK
中科院分区：
文献类型：
--
作者：
Moriwaki K;Chan FK
最近的研究发现，受体相互作用蛋白激酶1(RIPK1)、RIPK3和假性激酶混合谱系激活区样蛋白(MLKL)参与了一系列信号转导通路，这些信号通路在细胞死亡的一种非凋亡性形式--坏死性下垂的诱导中起着至关重要的作用。RIPK1-RIPK3-MLKL介导的坏死性下垂通过释放细胞损伤相关的分子模式(DAMP)而导致许多炎症性疾病。除了坏死性下垂，新出现的证据表明，这些坏死性下垂信号适配器也可以促进炎症，而不是细胞死亡。特别是，RIP激酶可以驱动NF-κB和炎症体的激活，而不依赖于细胞死亡。在这篇综述中，我们将讨论导致这一认识的最新发现，并提出为什么RIP激酶的细胞死亡非依赖性信号在炎症中可能比坏死性下垂具有更重要的作用。
Recent advances have identified a signaling cascade involving receptor interacting protein kinase 1 (RIPK1), RIPK3 and the pseudokinase mixed lineage kinase domain-like (MLKL) that is crucial for induction of necroptosis, a non-apoptotic form of cell death. RIPK1–RIPK3–MLKL-mediated necroptosis has been attributed to cause many inflammatory diseases through the release of cellular damage-associated molecular patterns (DAMPs). In addition to necroptosis, emerging evidence suggests that these necroptosis signal adaptors can also facilitate inflammation independent of cell death. In particular, the RIP kinases can drive NF-κB and inflammasome activation independent of cell death. In this review, we will discuss recent discoveries that led to this realization and present arguments why cell death-independent signaling by the RIP kinases may have a more important role in inflammation than necroptosis.