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首页> 外文期刊>Molecular and Cellular Biology >Lack of a role for Jun kinase and AP-1 in Fas-induced apoptosis.
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Lack of a role for Jun kinase and AP-1 in Fas-induced apoptosis.

机译：Jun激酶和AP-1在Fas诱导的细胞凋亡中缺乏作用。

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Cross-linking of Fas (CD95) induces apoptosis, a response that has been reported to depend upon the Ras activation pathway. Since many examples of apoptosis have been reported to involve AP-1 and/or the AP-1-activation pathway. Since many examples of apoptosis have been reported to involve AP-1 and/or the AP-1-activating enzyme Jun kinase (JNK), downstream effectors of Ras or Ras-like small GTP-binding proteins, we evaluated the role of these molecules in Fas-mediated apoptosis. Although cross-linking of Fas on Jurkat T cells did result in JNK activation, increased activity was observed relatively late, being detectable only after 60 min of stimulation. Expression of a dominant negative form of SEK1 that blocked Fas-mediated induction of JNK activity had no effect on Fas-mediated apoptosis. Furthermore, maximally effective concentrations of anti-Fas did not cause JNK activation if apoptosis was blocked by a cysteine protease inhibitor, suggesting that under these conditions, activation of JNK may be secondary to the stress of apoptosis rather than a direct result of Fas engagement. Despite the activation of JNK, there was no induction of AP-1 activity as determined by gel shift assay or induction of an AP-1-responsive reporter. The lack of a requirement for AP-1 induction in Fas-mediated death was further substantiated with Jurkat cells that were stably transfected with a dominant negative cJun, TAM-67. While TAM-67 effectively prevented AP-1-dependent transcription of both the interleukin-2 and cJun genes, it had no effect on Fas-induced cell death, even at limiting levels of Fas signaling. Thus, induction of JNK activity in Jurkat cells by ligation of Fas at levels sufficient to cause cell death is likely a result, rather than a cause, of the apoptotic response, and AP-1 function is not required for Fas-induced apoptosis.
机译：Fas（CD95）的交联诱导细胞凋亡，据报道这种反应取决于Ras激活途径。由于已经报道了许多凋亡的例子涉及AP-1和/或AP-1-激活途径。由于已经报道了许多凋亡的例子，涉及AP-1和/或AP-1激活酶Jun激酶（JNK），Ras或Ras样小GTP结合蛋白的下游效应子，因此我们评估了这些分子的作用Fas介导的细胞凋亡。尽管Fas在Jurkat T细胞上的交联确实导致JNK活化，但活性观察到的时间相对较晚，只有在刺激60分钟后才能检测到。阻断Fas介导的JNK活性诱导的SEK1显性负型表达对Fas介导的细胞凋亡没有影响。此外，如果凋亡被半胱氨酸蛋白酶抑制剂阻断，则最大有效浓度的抗Fas不会引起JNK激活，这表明在这些条件下，JNK的激活可能是继发于凋亡的应激之后的，而不是Fas参与的直接结果。尽管JNK的激活，但没有通过凝胶转移测定法或AP-1反应报告基因的诱导确定AP-1活性的诱导。 Fas介导的死亡中不需要AP-1诱导的需求进一步被Jurkat细胞证实，该细胞被显性阴性cTun TAM-67稳定转染。尽管TAM-67有效地阻止了白介素2和cJun基因的AP-1依赖性转录，但即使在Fas信号转导水平受到限制的情况下，它也对Fas诱导的细胞死亡没有影响。因此，通过以足以引起细胞死亡的水平连接Fas诱导Jurkat细胞中JNK活性的诱导可能是凋亡反应的结果而不是原因，并且Fas诱导的凋亡不需要AP-1功能。

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