Kang Jungseog, Yu Hongtao
Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
J Biol Chem. 2009 Jun 5;284(23):15359-63. doi: 10.1074/jbc.R900005200. Epub 2009 Feb 19.
The spindle checkpoint is a cell cycle surveillance system that ensures the fidelity of chromosome segregation. In mitosis, it elicits the "wait anaphase" signal to inhibit the anaphase-promoting complex or cyclosome until all chromosomes achieve bipolar microtubule attachment and align at the metaphase plate. Because a single kinetochore unattached to microtubules activates the checkpoint, the wait anaphase signal is thought to be generated by this kinetochore and is then amplified and distributed throughout the cell to inhibit the anaphase-promoting complex/cyclosome. Several spindle checkpoint kinases participate in the generation and amplification of this signal. Recent studies have begun to reveal the activation mechanisms of these checkpoint kinases. Increasing evidence also indicates that the checkpoint kinases not only help to generate the wait anaphase signal but also actively correct kinetochore-microtubule attachment defects.
纺锤体检查点是一种细胞周期监测系统,可确保染色体分离的准确性。在有丝分裂过程中,它引发“等待后期”信号,以抑制后期促进复合物或细胞周期体,直到所有染色体实现双极微管附着并排列在中期板上。由于单个未附着微管的动粒会激活检查点,因此人们认为“等待后期”信号是由该动粒产生的,然后在整个细胞中放大并传播,以抑制后期促进复合物/细胞周期体。几种纺锤体检查点激酶参与了该信号的产生和放大。最近的研究开始揭示这些检查点激酶的激活机制。越来越多的证据还表明,检查点激酶不仅有助于产生“等待后期”信号,还能积极纠正动粒-微管附着缺陷。