ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis.
ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis.
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发表时间：
2003
影响因子：
3.1
通讯作者：
J. Masumoto;T. A. Dowds;P. Schaner;Felicia F. Chen;Y. Ogura;Mu Li;Li Zhu;T. Katsuyama;J. Sagara;S. Taniguchi;D. Gumucio;G. Núñez;N. Inohara
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作者：
J. Masumoto;T. A. Dowds;P. Schaner;Felicia F. Chen;Y. Ogura;Mu Li;Li Zhu;T. Katsuyama;J. Sagara;S. Taniguchi;D. Gumucio;G. Núñez;N. Inohara
ASC是一种促凋亡蛋白，含有pyrin结构域（PD）和半胱天冬酶募集结构域（CARD）。先前的研究表明ASC与Apaf-1/Nod 1蛋白家族成员Ipaf相互作用。然而，相互作用的功能相关性尚未确定。在此，我们报道了ASC与Ipaf的共表达或ASC的寡聚化诱导细胞凋亡和NF-κ B活化。通过ASC诱导的细胞凋亡被Caspase-8的突变形式抑制，但不被Caspase-1抑制。ASC的PD与Caspase-8以及家族性地中海热基因产物pyrin相互作用。Caspase-8缺陷从ASC寡聚化诱导的凋亡中拯救小鼠成纤维细胞。Pyrin阻断ASC与Caspase-8的相互作用，抑制ASC诱导的细胞凋亡和NF-κ B B活化。这些发现表明ASC是Ipaf信号通路中NF-κ B活化和Caspase-8依赖性凋亡的介导者。
ASC is a pro-apoptotic protein containing a pyrin domain (PD) and a caspase-recruitment domain (CARD). A previous study suggests that ASC interacts with Ipaf, a member of the Apaf-1/Nod1 protein family. However, the functional relevance of the interaction has not been determined. Here, we report that co-expression of ASC with Ipaf or oligomerization of ASC induces both apoptosis and NF-kappa B activation. Apoptosis induced through ASC was inhibited by a mutant form of Caspase-8 but not by that of Caspase-1. The PD of ASC physically interacted with Caspase-8 as well as with pyrin, the familial Mediterranean fever gene product. Caspase-8 deficiency rescued mouse fibroblasts from apoptosis induced by ASC oligomerization. Pyrin disrupted the interaction between ASC and Caspase-8, and inhibited both apoptosis and NF-kappa B activation induced by ASC. These findings suggest that ASC is a mediator of NF-kappa B activation and Caspase-8-dependent apoptosis in an Ipaf signaling pathway.