通过CENP-E依赖的BubR1的激活/非激活来激活和静止线粒检查点
Yinghui Mao1, Ariane Abrieu, Don W Cleveland
1Ludwig Institute for Cancer Research, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cell
|July 16, 2003
概括
线粒检查点确保了正确的染色体附着. 研究人员发现,CENP-E激活了BubR1激酶,并在附着后使其沉默,揭示了BubR1激酶.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 线粒检查点对于精确的染色体分离至关重要.
- 它阻止了亚纳相的发生,直到所有的染色体正确地附着在线索微管中.
- 在这个检查点路径中,BubR1是必不可少的激酶.
研究的目的:
- 阐明CENP-E在调节线性检查点激酶BubR1.1.中的作用.
- 了解BubR1活动在线粒分裂期间是如何控制的.
- 调查BubR1在检查点信号中的双功能作用.
主要方法:
- 使用了纯化的蛋白质成分.
- 在体外研究中使用了Xenopus蛋提取物.
- 研究了CENP-E抗体对BubR1活性的影响.
主要成果:
- 运动关联电机CENP-E激活了BubR1激酶.
- 在微管附着时,CENP-E调解了BubR1信号的沉默.
- BubR1 需要其 Mad3 域进行 Cdc20 结合,但只有一小部分需要酶活性.
结论:
- 在线粒检查点中,CENP-E扮演着双重的角色:激活和沉默BubR1.1.
- 布布R1的功能既是酶的 (激酶活性),也是固态的 (Cdc20抑制).
- 这项研究揭示了线粒体检查点控制的新型调节机制.
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