Activation of apoptosis signal regulating kinase 1 (ASK1) by the adapter protein Daxx
Activation of apoptosis signal regulating kinase 1 (ASK1) by the adapter protein Daxx
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DOI：
10.1126/science.281.5384.1860
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发表时间：
1998-09-18
期刊：
影响因子：
56.9
通讯作者：
Baltimore, D
中科院分区：
文献类型：
--
作者：
Chang, HY;Nishitoh, H;Baltimore, D
Fas死亡受体可以通过受体相关蛋白Daxx激活Jun NH 2-末端激酶（JNK）途径。Daxx被发现激活JNK激酶激酶ASK 1，激酶缺陷型ASK 1突变体的过表达抑制Fas和Daxx诱导的细胞凋亡和JNK激活。Fas激活诱导Daxx与ASK 1相互作用，从而解除ASK 1的氨基和羧基末端之间的抑制性分子内相互作用，激活其激酶活性。Daxx-ASK 1连接完成了从细胞表面死亡受体到调节核转录因子的激酶级联的信号通路。
The Fas death receptor can activate the Jun NH2-terminal kinase (JNK) pathway through the receptor-associated protein Daxx. Daxx was found to activate the JNK kinase kinase ASK1, and overexpression of a kinase-deficient ASK1 mutant inhibited Fas- and Daxx-induced apoptosis and JNK activation. Fas activation induced Daxx to interact with ASK1, which consequently relieved an inhibitory intramolecular interaction between the amino- and carboxyl-termini of ASK1, activating its kinase activity. The Daxx-ASK1 connection completes a signaling pathway from a cell surface death receptor to kinase cascades that modulate nuclear transcription factors.