PKCη confers protection against apoptosis by inhibiting the pro-apoptotic JNK activity in MCF-7 cells
PKCη confers protection against apoptosis by inhibiting the pro-apoptotic JNK activity in MCF-7 cells
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DOI：
10.1016/j.yexcr.2009.06.004
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发表时间：
2009-09-10
影响因子：
3.7
通讯作者：
Livneh, Etta
中科院分区：
文献类型：
--
作者：
Rotem-Dai, Noa;Oberkovitz, Galia;Livneh, Etta
细胞凋亡通常受不同的蛋白激酶的调节，包括蛋白激酶C家族的酶。对几种不同的PKC亚型既有抑制作用，又有刺激作用。在这里，我们发现了新的PKC亚型PKC ETA，对DNA损伤剂UVC照射和抗癌药物喜树碱诱导的乳腺上皮腺癌MCF-7细胞的凋亡具有保护作用。在四环素反应启动子的控制下，在MCF-7细胞中诱导PKC ETA的表达，导致细胞存活率增加，并抑制了凋亡标记物PARP-1的切割。PKC ETA的诱导表达也抑制了caspase-7和caspase-9的激活以及细胞色素c的释放。此外，JNK活性也被PKC抑制，该活性是MCF-7细胞凋亡所必需的，表现为在存在JNK抑制剂SP600125的情况下，抑制线粒体caspase-7的切割和细胞色素c的释放。表情。因此，与大多数促进JNK活性的PKC亚型不同，我们的研究表明，PKC ETA是一种抗凋亡蛋白，起到JNK活性的负调节作用。因此，PKC。可能代表了旨在减少抗癌治疗耐药性的干预目标。(C)2009 Elsevier Inc.保留所有权利。
Apoptosis is frequently regulated by different protein kinases including protein kinase C family enzymes. Both inhibitory and stimulatory effects were demonstrated for several of the different PKC isoforms. Here we show that the novel PKC isoform, PKC eta, confers protection against apoptosis induced by the DNA damaging agents, UVC irradiation and the anti-cancer drug-Camptothecin, of the breast epithelial adenocarcinoma MCF-7 cells. The induced expression of PKC eta in MCF-7 cells, under the control of the tetracycline-responsive promoter, resulted in increased cell survival and inhibition of cleavage of the apoptotic marker PARP-1. Activation of caspase-7 and 9 and the release of cytochrome c were also inhibited by the inducible expression of PKC eta. Furthermore, JNK activity, required for apoptosis in MCF-7, as indicated by the inhibition of both caspase-7 cleavage and cytochrome c release from the mitochondria in the presence of the JNK inhibitor SP600125, was also suppressed by PKC. expression. Hence, in contrast to most PKC isoforms enhancing JNK activation, our studies show that PKC eta is an anti-apoptotic protein, acting as a negative regulator of JNK activity. Thus, PKC. could represent a target for intervention aimed to reduce resistance to anti-cancer treatments. (C) 2009 Elsevier Inc. All rights reserved.