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首页> 外文期刊>Cell cycle >Cyclin B1 interacts with the BH3-only protein Bim and mediates its phosphorylation by Cdk1 during mitosis.
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Cyclin B1 interacts with the BH3-only protein Bim and mediates its phosphorylation by Cdk1 during mitosis.

机译：细胞周期蛋白B1与仅BH3的蛋白Bim相互作用，并在有丝分裂期间通过Cdk1介导其磷酸化。

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Protracted mitotic arrest leads to cell death; however, the molecular signals that link these distinct processes remain poorly understood. Here we report that the pro-apoptotic BH3-only family member Bim undergoes phosphorylation in K562 cells following treatment with the microtubule targeting agents Taxol and Nocodazole. The phosphorylation of two Bim isoforms, BimEL and BimL, at the mitochondria correlates with mitotic arrest and precedes cell death induced by Taxol. It was also found that Bim undergoes transient phosphorylation during normal mitosis in K562 cells. In addition, siRNA silencing of Bim reduces sensitivity to Taxol-induced cell death. The transition of K562 cells from mitosis to G1 results in the loss of BimEL and BimL phosphorylation and correlates with the degradation of cyclin B1. The Cdk1 inhibitors, RO-3306 and Purvalanol A, block Bim phosphorylation in mitotically arrested cells. Importantly, it was found that cyclin B1 co-immunoprecipitates with endogenous Bim in mitotic extracts. Furthermore, active recombinant Cdk1/cyclin B1 phosphorylates BimEL and BimL in vitro and Serine 44 on BimL has been identified as a Cdk1 phosphorylation site. Collectively, these results suggest that Cdk1/cyclin B1-dependent hyper-phosphorylation of Bim during prolonged mitotic arrest is an important cell death signal.
机译：长时间的有丝分裂阻滞导致细胞死亡;然而，连接这些不同过程的分子信号仍然知之甚少。在这里我们报告说，用微管靶向剂紫杉醇和诺考达唑治疗后，促凋亡的仅BH3家族成员Bim在K562细胞中发生磷酸化。线粒体上两种Bim亚型BimEL和BimL的磷酸化与有丝分裂阻滞有关，并在由紫杉醇诱导的细胞死亡之前发生。还发现Bim在正常的K562细胞有丝分裂过程中经历了短暂的磷酸化。另外，Bim的siRNA沉默降低了对紫杉醇诱导的细胞死亡的敏感性。 K562细胞从有丝分裂过渡到G1导致BimEL和BimL磷酸化的丧失，并与细胞周期蛋白B1的降解有关。 Cdk1抑制剂RO-3306和Purvalanol A阻止有丝分裂阻滞细胞中的Bim磷酸化。重要的是，发现细胞周期蛋白B1与有丝分裂提取物中的内源性Bim共同免疫沉淀。此外，活性重组Cdk1 / cyclin B1在体外使BimEL和BimL磷酸化，BimL上的丝氨酸44被鉴定为Cdk1磷酸化位点。总体而言，这些结果表明，在有丝分裂长时间停止期间，Bim的Cdk1 / cyclin B1依赖性Bim过度磷酸化是重要的细胞死亡信号。

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