Chang H Y, Nishitoh H, Yang X, Ichijo H, Baltimore D
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02138, USA.
Science. 1998 Sep 18;281(5384):1860-3. doi: 10.1126/science.281.5384.1860.
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.
Fas死亡受体可通过受体相关蛋白Daxx激活Jun氨基末端激酶（JNK）信号通路。研究发现，Daxx可激活JNK激酶激酶ASK1，而激酶缺陷型ASK1突变体的过表达可抑制Fas和Daxx诱导的细胞凋亡及JNK激活。Fas激活可诱导Daxx与ASK1相互作用，从而解除ASK1分子内氨基末端和羧基末端之间的抑制性相互作用，激活其激酶活性。Daxx与ASK1的联系完善了一条从细胞表面死亡受体到调节核转录因子的激酶级联反应的信号通路。
