Hardwick K G, Weiss E, Luca F C, Winey M, Murray A W
Department of Physiology, University of California, San Francisco, CA 94143-0444, USA.
Science. 1996 Aug 16;273(5277):953-6. doi: 10.1126/science.273.5277.953.
The spindle assembly checkpoint keeps cells with defective spindles from initiating chromosome segregation. The protein kinase Mps1 phosphorylates the yeast protein Mad1p when this checkpoint is activated, and the overexpression of Mps1p induces modification of Mad1p and arrests wild-type yeast cells in mitosis with morphologically normal spindles. Spindle assembly checkpoint mutants overexpressing Mps1p pass through mitosis without delay and can produce viable progeny, which demonstrates that the arrest of wild-type cells results from inappropriate activation of the checkpoint in cells whose spindle is fully functional. Ectopic activation of cell-cycle checkpoints might be used to exploit the differences in checkpoint status between normal and tumor cells and thus improve the selectivity of chemotherapy.
纺锤体组装检查点可防止具有缺陷纺锤体的细胞启动染色体分离。当该检查点被激活时，蛋白激酶Mps1会使酵母蛋白Mad1p磷酸化，并且Mps1p的过表达会诱导Mad1p的修饰，并使野生型酵母细胞在有丝分裂期停滞，纺锤体形态正常。过表达Mps1p的纺锤体组装检查点突变体可毫无延迟地通过有丝分裂并产生可存活的后代，这表明野生型细胞的停滞是由于纺锤体功能完全正常的细胞中检查点的不适当激活所致。细胞周期检查点的异位激活可用于利用正常细胞和肿瘤细胞之间检查点状态的差异，从而提高化疗的选择性。
