Thymoquinone disrupts the microtubule dynamics in fission yeast Schizosaccharomyces pombe

N. Masood, Saman Khan, S. Luqman, Shakil Ahmed
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Abstract

Abstract 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.
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百里醌破坏裂糖酵母的微管动力学
摘要研究发现裂糖酵母(Schizosaccharomyces pombe)的Mad2缺失菌株对黑草(Nigella sativa)中的特征分子百里醌(thymo醌)敏感,并呈剂量依赖性。Mad2蛋白是有丝分裂纺锤体检查点复合体不可缺少的组成部分,是响应纺锤体缺陷的细胞周期阻滞所必需的。虽然在百里醌处理的细胞中α微管蛋白的表达不受影响,但β微管蛋白的表达降低。此外,百里醌处理的细胞中微管的缺失表明其参与微管蛋白聚合。分子对接研究发现,百里醌在Tub1 (Tubulin α-β二聚体)Taxotere结合位点附近特异性结合β-微管蛋白。这些研究还表明,百里醌与链B中的残基相互作用,而链B是有丝分裂检查点复合体(MCC)的Mad2蛋白的固有部分。我们得出结论,百里醌破坏微管聚合,导致梭形检查点蛋白对细胞生存的需求。
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AIMS Genetics
AIMS Genetics GENETICS & HEREDITY-
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