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Biological events and molecular signaling following MLKL activation during necroptosis

机译:在虐疮期间MLKL活化后的生物事件和分子信号

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摘要

Necroptosis is a form of programmed necrotic cell death mediated by the kinase RIPK3 and its substrate MLKL. MLKL, which displays plasma membrane (PM) pore-forming activity upon phosphorylation, functions as the executionerduring necroptosis. Thus, it was previously assumed that MLKL phosphorylation is the endpoint of the necroptotic signaling pathway. Here, we summarize several events that characterize the dying necroptotic cells after MLKL phosphorylation, including Ca2+ influx, phosphatidylserine (PS) externalization, PM repair by ESCRT-III activation, and the final compromise of PM integrity. These processes add several unexpected regulatory events downstream of MLKL signaling. We have also observed that CoCl2, which may mimic hypoxia, can induce necroptosis, which suggests that in vivo triggers of necroptosis might include a transient lack of O-2.
机译:Necroptis是由激酶RIPK3介导的编程坏死性细胞死亡的一种形式及其基材MLK1。 在磷酸化上显示血浆膜(PM)孔隙形成活性的MLK1,用作脱震粪便。 因此,预先假设MLK1磷酸化是恶臭信号传导途径的终点。 在这里,我们总结了在MLK1磷酸化后表征染色的恶臭细胞的几个事件,包括Ca2 +流入,磷脂酰丝氨酸(PS)外化,PM通过ESCRT-III活化修复,以及PM完整性的最终折衷。 这些过程在MLKL信令下游添加了几个意想不到的监管事件。 我们还观察到可模仿缺氧的Cocl2可以诱导死亡症,这表明在虐疮的体内触发中可能包括暂时缺乏O-2。

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