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首页> 外文期刊>EMBO Journal >Palmitoylation of CD95 facilitates formation of SDS-stable receptor aggregates that initiate apoptosis signaling
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Palmitoylation of CD95 facilitates formation of SDS-stable receptor aggregates that initiate apoptosis signaling

机译:棕榈酰化的CD95促进形成启动SDS-stable受体聚集细胞凋亡信号

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摘要

Apoptosis signaling through CD95 (Fas/APO-1) involves aggregation and clustering of the receptor followed by its actin-dependent internalization. Internalization is required for efficient formation of the death-inducing signaling complex (DISC) with maximal recruitment of FADD, caspase-8/ 10 and c-FLIP occurring when the receptor has reached an endosomal compartment. The first detectable event during CD95 signaling is the formation of SDS-stable aggregates likely reflecting intense oligomerization of the receptor. We now demonstrate that these SDS-stable forms of CD95 correspond to very high molecular weight DISC complexes (hiDISC) and are the sites of caspase-8 activation. hiDISCs are found both inside and outside of detergent-resistant membranes. The formation of SDS-stable CD95 aggregates involves palmitoylation of the membrane proximal cysteine 199 in CD95. Cysteine 199 mutants no longer form SDS-stable aggregates, and inhibition of palmitoylation reduces internalization of CD95 and activation of caspase-8. Our data demonstrate that SDS-stable forms of CD95 are the sites of apoptosis initiation and represent an important early step in apoptosis signaling through CD95 before activation of caspases.
机译:细胞凋亡信号通过CD95 (Fas / APO-1)包括聚合和集群的受体的actin-dependent紧随其后内化。death-inducing的有效形成信号复杂(盘)和最大的招聘FADD、caspase-8 / 10和c-FLIP时发生受体已达到一个endosomal隔间。CD95信号是SDS-stable的形成总量可能反映强烈齐聚反应的受体。证明这些SDS-stable CD95形式对应于高分子量盘配合物(hiDISC)和是caspase-8的场所激活。detergent-resistant外膜。形成SDS-stable CD95总量包括棕榈酰化膜的近半胱氨酸199年的CD95。SDS-stable聚集,抑制棕榈酰化减少CD95内化caspase-8和激活。SDS-stable CD95形式的网站细胞凋亡启动和代表一个重要细胞凋亡信号通过CD95早一步激活之前还存在。

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