MEKK1 is essential for DT40 cell apoptosis in response to microtubule disruption
MEKK1 is essential for DT40 cell apoptosis in response to microtubule disruption
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DOI：
10.1128/mcb.21.21.7183-7190.2001
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发表时间：
2001-11-01
影响因子：
5.3
通讯作者：
Cheng, GH
中科院分区：
文献类型：
--
作者：
Kwan, R;Burnside, J;Cheng, GH
长春碱和其他微管损伤剂，如诺考达唑和紫杉醇，导致细胞周期停滞在G（2）/M转换，并促进真核细胞凋亡。这些药物在破坏微管动力学和引起细胞周期停滞中的作用得到了很好的表征。然而，这些药物促进细胞凋亡的机制知之甚少。我们通过同源重组破坏了鸡法氏囊B细胞系DT 40中的MEKK 1激酶结构域，并表明它对长春碱介导的细胞凋亡和长春碱介导的c-jun N-末端蛋白激酶激活都是必不可少的。此外，我们的数据表明，长春碱介导的DT 40细胞凋亡需要新的蛋白质合成，但不需要G（2）/M阻滞，表明长春碱介导的细胞周期阻滞和凋亡是两个独立的过程。
Vinblastine and other microtubule-damaging agents, such as nocodazole and paclitaxel, cause cell cycle arrest at the G(2)/M transition and promote apoptosis in eukaryotic cells. The roles of these drugs in disrupting microtubule dynamics and causing cell cycle arrest are well characterized. However, the mechanisms by which these agents promote apoptosis are poorly understood. We disrupted the MEKK1 kinase domain in chicken bursal B-cell line DT40 by homologous recombination and have shown that it is essential for both vinblastine-mediated apoptosis and vinblastine-mediated c-jun N-terminal protein kinase activation. In addition, our data indicate that vinblastine-mediated apoptosis in DT40 cells requires new protein synthesis but does not require G(2)/M arrest, suggesting that vinblastine-mediated cell cycle arrest and apoptosis are two independent processes.