Palmitoylation is required for efficient Fas cell death signaling
Palmitoylation is required for efficient Fas cell death signaling
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DOI：
10.1038/sj.emboj.7601456
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发表时间：
2007-01-10
期刊：
影响因子：
11.4
通讯作者：
Hueber, Anne-Odile
中科院分区：
文献类型：
--
作者：
Chakrabandhu, Krittalak;Herincs, Zoltan;Hueber, Anne-Odile
死亡受体Fas定位于专门的膜微区对Fas介导的细胞死亡信号传导至关重要。在这里，我们报告的翻译后修饰Fas的棕榈酰化在膜近端的半胱氨酸残基在胞质区域是Fas定位到脂筏的靶向信号，在无细胞和活细胞系统中证明。棕榈酰化是Fas刺激后Fas重新分配到肌动蛋白细胞骨架连接筏和筏依赖性ezrin介导的细胞骨架缔合所必需的，这对于有效的Fas受体内化、诱导死亡的信号复合物组装和随后的导致细胞死亡的caspase级联反应是必需的。
Localization of the death receptor Fas to specialized membrane microdomains is crucial to Fas-mediated cell death signaling. Here, we report that the post-translational modification of Fas by palmitoylation at the membrane proximal cysteine residue in the cytoplasmic region is the targeting signal for Fas localization to lipid rafts, as demonstrated in both cell-free and living cell systems. Palmitoylation is required for the redistribution of Fas to actin cytoskeleton-linked rafts upon Fas stimulation and for the raft-dependent, ezrin-mediated cytoskeleton association, which is necessary for the efficient Fas receptor internalization, death-inducing signaling complex assembly and subsequent caspase cascade leading to cell death.