细胞分裂周期. MPS1和微管在kinetochores之间的竞争调节了螺旋检查点信号传输
Yoshitaka Hiruma1, Carlos Sacristan2, Spyridon T Pachis2
1Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands.
Science (New York, N.Y.)
|June 13, 2015
概括
螺旋组装检查点蛋白激酶MPS1与NDC80复合体相互作用,防止细胞分裂,直到染色体附着于微管. 微管附着物破坏了这种相互作用,确保了细胞分裂的正确组织.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细胞分裂需要适当的染色体螺旋连接,由螺旋组装检查点 (SAC) 监控.
- 该NDC80复合体是一个关键的kinetochore组件介导微管附着.
- MPS1是一种关键的SAC蛋白激酶,参与调节细胞周期进展.
研究的目的:
- 研究MPS1与NDC80复合体相互作用的分子机制.
- 确定微管附着如何影响MPS1-NDC80相互作用.
- 阐明这种相互作用在SAC和细胞分裂调节中的作用.
主要方法:
- 在体外结合测试以研究蛋白质-蛋白质相互作用.
- 酸化试验用于评估酸化在相互作用中的作用.
- 基于细胞的实验使用异位表达和显微镜观察蛋白质局部化和结合 in vivo.
- 微管束结合测试.微管束结合测试.
主要成果:
- MPS1的氨基末端定位模块直接与NDC80复合体内的HEC1的calponin同质域相互作用.
- 这种相互作用是依赖酸化的.
- 微管聚合物在体外破坏MPS1-NDC80的相互作用.
- 末端的微管附着在kinetochores上,防止MPS1在细胞中结合,独立于已知的蛋白质去除机制.
结论:
- MPS1与kinetochore结合是通过微管附着直接调节的.
- 这种SAC蛋白和微管之间竞争的kinetochore结合提供了一个检测正确组织的螺旋的机制.
- 这种相互作用是一种直接的和潜在的保存机制,以确保精确的细胞分裂.
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