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Thymoquinone disrupts the microtubule dynamics in fission yeast Schizosaccharomyces pombe

机译:胸腺醌破坏裂殖酵母裂殖酵母的微管动力学

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Mad2 deletion strain of Schizosaccharomyces pombe was found to be sensitive to thymoquinone, a signature molecule present in Nigella sativa in a dose-dependent manner. Mad2 protein is an indispensable part of mitotic spindle checkpoint complex and is required for the cell cycle arrest in response to the spindle defects. Although the expression of α tubulin was not affected in thymoquinone treated cells, but the expression of β-tubulin was reduced. Further, the absence of microtubule in thymoquinone treated cells suggests its involvement in tubulin polymerization. Molecular docking studies revealed that thymoquinone specifically binds to β-tubulin near the Taxotere binding site of Tub1 (Tubulin α-β dimer). These studies additionally showed that thymoquinone interacts with the residues present in chain B, which is an inherent part of Mad2 protein of mitotic checkpoint complex (MCC). We concluded that the thymoquinone disrupts the microtubule polymerization that leads to the requirement of spindle checkpoint protein for the cell survival.
机译:发现粟酒裂殖酵母的Mad2缺失菌株对胸腺醌敏感,胸腺醌是一种以剂量依赖的方式存在于黑夜蛾中的标志性分子。 Mad2蛋白是有丝分裂纺锤体检查点复合物的必不可少的部分,是响应纺锤体缺陷而停止细胞周期所必需的。尽管在胸腺醌处理的细胞中α微管蛋白的表达不受影响,但是β-微管蛋白的表达降低。此外,胸腺醌处理的细胞中不存在微管,提示其参与了微管蛋白聚合反应。分子对接研究表明,胸腺醌与Tub1(Tubulinα-β二聚体)的Taxotere结合位点附近的β-微管蛋白特异性结合。这些研究还表明,胸腺醌与链B中存在的残基相互作用,后者是有丝分裂检查点复合物(MCC)Mad2蛋白的固有部分。我们得出的结论是,胸腺醌干扰了微管聚合反应,导致细胞存活需要纺锤体检查点蛋白。

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