Abstract
AbstractMad2 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.
Highlights
Schizosaccromyces pombe come up to an elevated level of perpetuation in cellular processes mimicking mammalian cells with numerous advantages including simple growth requirements, rapid cell division and ease of genetic maneuvring [1]
These studies showed that thymoquinone interacts with the residues present in chain B, which is an inherent part of Mad2 protein of mitotic checkpoint complex (MCC)
While cells containing vector control were growing well on all the plates (Figure 6). These results suggest that the binding of TQ with the proteins required for spindle assembly checkpoint pathway (Mad2 and Bub3) might be responsible for growth defect
Summary
Schizosaccromyces pombe come up to an elevated level of perpetuation in cellular processes mimicking mammalian cells with numerous advantages including simple growth requirements, rapid cell division and ease of genetic maneuvring [1]. SAC is a conserved surveillance mechanism that arrests cells in mitosis in response to malfunctioning spindle [7]. The core proteins involved in SAC are Bub, Bub, Mad, Mad and Mad3 [10,11]. These proteins are responsible for regulating Anaphase Promoting Complex (APC) activity. The S. pombe SAC protein Mad interacts with APC and blocks anaphase. In S. pombe, Mad over-expression imitates activation of the SAC and results in the arrest of cell cycle at the metaphase-anaphase transition [15,16]. Inhibition of Mad or BubR1 checkpoint proteins in aneuploid cancer cells restrains pathways necessary to maintain CIN [18]
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