Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product
Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product
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DOI：
10.1016/s0006-291x(03)00221-3
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发表时间：
2003-03-14
影响因子：
3.1
通讯作者：
Núñez, G
中科院分区：
文献类型：
--
作者：
Dowds, TA;Masumoto, J;Núñez, G
Cryopyrin 是 Nod 蛋白家族的成员，在家族性寒冷性荨麻疹和 Muckle-Wells 综合征中发生突变，最近与炎症有关。然而，冷吡蛋白信号通路的激活和调节机制仍然知之甚少。我们在此报告，冷吡蛋白与其结合伴侣 ASC 的共表达诱导细胞凋亡和 NF-κB 激活。这种信号传导被 ASC 的寡聚化所模仿，表明冷冻蛋白激活下游靶标，正如其他 Nod 家族成员所报道的那样。值得注意的是，pyrin（家族性地中海热基因的产物）通过破坏 Cryopyrin-ASC 相互作用来抑制 Cryopyrin 介导的细胞凋亡和 NF-κB 激活。这些结果为冷热蛋白信号通路通过 ASC 的诱导接近而激活提供了证据，而 ASC 受到热蛋白的负调节。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
Cryopyrin, a member of the Nod protein family mutated in familial cold urticaria and Muckle-Wells syndrome, has been recently implicated in inflammation. However, the mechanism of activation and regulation of the cryopyrin signaling pathway remains poorly understood. We report here that co-expression of cryopyrin with its binding partner, ASC, induced both apoptosis and NF-kappaB activation. This signaling was mimicked by oligomerization of ASC, suggesting that cryopyrin activates downstream targets as reported for other Nod family members. Notably, pyrin, the product of the familial Mediterranean fever gene, inhibited cryopyrin-mediated apoptosis and NF-kappaB activation by disrupting the cryopyrin-ASC interaction. These results provide evidence for a cryopyrin signaling pathway activated through the induced proximity of ASC, which is negatively regulated by pyrin. (C) 2003 Elsevier Science (USA). All rights reserved.