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首页> 外文期刊>Cell cycle >Chromium induces chromosomal instability, which is partly due to deregulation of BubR1 and Emi1, two APC/C inhibitors.
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Chromium induces chromosomal instability, which is partly due to deregulation of BubR1 and Emi1, two APC/C inhibitors.

机译：铬诱导染色体不稳定，部分原因是由于两种APC / C抑制剂BubR1和Emi1的失控。

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Disruption of cell cycle checkpoints and interference with the normal cell cycle progression frequently result in cell death or malignant transformation. Hexavalent chromium [Cr(VI)] is a well-known carcinogen that has been implicated in the occurrence of many types of human malignancies, including lung cancer. However, the exact mechanism by which Cr(VI) causes malignant transformation in the lung remains unknown. We have demonstrated that chronic exposure to a non-cytotoxic concentration of Cr(VI) induced a variety of chromosomal abnormalities, including premature sister chromatid separation, chromosomal breakage and the presence of lagging/misaligned chromosomes. After treatment with nocodazole, both HeLa and normal lung bronchial epithelial cells were arrested at mitosis. However, Cr(VI) significantly compromised M-phase arrest induced by nocodazole. Cr(VI) suppressed BubR1 activation and reduced expression of Emi1, leading to an unscheduled activation of APC/C. Consistent with this observation, Cr(VI) treatment caused enhanced polyubiquitination of geminin during mitotic release, while it deregulated the activity of Cdt1, a DNA replication licensing factor. Combined, these results suggest that Cr(VI)-induced chromosomal instability is partly due to a perturbation of APC/C activities, leading to chromosomal instability.
机译：细胞周期检查点的破坏和对正常细胞周期进程的干扰经常导致细胞死亡或恶性转化。六价铬[Cr（VI）]是一种众所周知的致癌物，与多种类型的人类恶性肿瘤（包括肺癌）有关。然而，Cr（VI）引起肺部恶性转化的确切机制仍然未知。我们已经证明，长期暴露于非细胞毒性浓度的Cr（VI）会引起各种染色体异常，包括早熟姐妹染色单体分离，染色体断裂和染色体滞后/错位。用诺考达唑治疗后，HeLa和正常肺支气管上皮细胞均在有丝分裂时停滞。但是，Cr（VI）大大损害了由诺考达唑引起的M相阻滞。 Cr（VI）抑制BubR1激活并减少Emi1的表达，从而导致APC / C的计划外激活。与该观察结果一致，Cr（VI）处理在有丝分裂释放过程中引起了双倍的双倍体蛋白双倍泛素化，同时它取消了DNA复制许可因子Cdt1的活性。结合起来，这些结果表明Cr（VI）诱导的染色体不稳定性部分是由于APC / C活性的扰动，导致染色体不稳定性。

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