Transient stimulation of the c-Jun-NH2-terminal kinase/activator protein 1 pathway and inhibition of extracellular signal-regulated kinase are early effects in paclitaxel-mediated apoptosis in human B lymphoblasts.
Transient stimulation of the c-Jun-NH2-terminal kinase/activator protein 1 pathway and inhibition of extracellular signal-regulated kinase are early effects in paclitaxel-mediated apoptosis in human B lymphoblasts.
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发表时间：
1998-01
期刊：
影响因子：
11.2
通讯作者：
S. F. Amato;J. M. Swart;M. Berg;H. Wanebo;S. R. Mehta;T. Chiles
中科院分区：
文献类型：
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作者：
S. F. Amato;J. M. Swart;M. Berg;H. Wanebo;S. R. Mehta;T. Chiles
我们在这里证明紫杉醇暴露于rpm -1788 B淋巴细胞导致核因子激活蛋白1 (AP-1) DNA结合活性的剂量和时间依赖性增加。核因子NF-kappaB和Ets的基础DNA结合活性不受紫杉醇影响。与这些生化事件一致，紫杉醇刺激ap -1依赖性氯霉素乙酰转移酶（CAT）报告基因在体内的转录，由十四烷醇醋酸磷诱导启动子引导。紫杉醇处理细胞的核提取物的AP-1结合活性在针对单个Jun家族蛋白的抗体免疫消耗后降低，而抗cfos、抗fra1和抗fosb抗体没有抑制作用。紫杉醇引起c-Jun nh2末端激酶（JNK）活性的快速和短暂增加，这是一种被提出的应激激活途径的介质。相比之下，暴露于紫杉醇会导致细胞外信号调节的丝裂原活化蛋白激酶2 （ERK2）活性的短暂降低，ERK2是一种生长因子刺激的增殖途径的介质。c- jun - nh2末端激酶/AP-1通路的短暂激活，以及ERK2活性的下调，可能是rpm -1788 B淋巴细胞对紫杉醇暴露早期反应的关键事件。
We demonstrate here that paclitaxel exposure to RPMI-1788 B lymphoblasts caused a dose- and time-dependent increase in nuclear factor activator protein 1 (AP-1) DNA binding activity. The basal DNA binding activities of nuclear factors NF-kappaB and Ets were not affected by paclitaxel. Consistent with these biochemical events, paclitaxel stimulated AP-1-dependent chloramphenicol acetyltransferase (CAT) reporter gene transcription in vivo, as directed from a tetradecanoyl phorbol acetate-inducible promoter. AP-1 binding activity of nuclear extracts isolated from paclitaxel treated cells was reduced following immunodepletion with antibodies directed against individual Jun family proteins, whereas anti-cFos, anti-Fra1, and anti-FosB antibodies were not inhibitory. Paclitaxel caused a rapid and transient increase in c-Jun NH2-terminal kinase (JNK) activity, a proposed mediator of stress activation pathways. By contrast, exposure to paclitaxel produced a transient reduction in the extracellular signal-regulated mitogen-activated protein kinase 2 (ERK2) activity, a proposed mediator of growth factor-stimulated proliferation pathways. Transient activation of the c-Jun-NH2-terminal kinase/AP-1 pathway, together with down-regulation of ERK2 activity, may be a key event in the early response of RPMI-1788 B lymphoblasts to paclitaxel exposure.