Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, University of Leuven, B-3000 Leuven, Belgium.
Curr Biol. 2011 Nov 8;21(21):R898-903. doi: 10.1016/j.cub.2011.08.063.
The spindle checkpoint is a mitotic surveillance mechanism that delays anaphase until all sister chromatids are correctly attached to microtubules from opposite poles. Recent studies reveal that protein kinase Aurora B is a key regulator of spindle checkpoint activation whereas protein phosphatase PP1 antagonizes Aurora B and induces checkpoint silencing. Chromosome biorientation stretches the kinetochores and spatially separates centromeric Aurora B from its kinetochore substrates, comprising several PP1-interacting proteins (PIPs). The ensuing dephosphorylation of these PIPs creates docking sites for the bulk recruitment of PP1 to the kinetochores. We propose that this tension-induced targeting of PP1 triggers checkpoint silencing by the dephosphorylation of kinetochore and checkpoint components, including Aurora B substrates. In addition, PP1 also directly inactivates a kinetochore-associated pool of Aurora B and silences checkpoint signaling by opposing the centromeric targeting of Aurora B.
纺锤体检查点是一种有丝分裂监测机制，它会延迟后期，直到所有姐妹染色单体都正确地连接到来自相反极的微管上。最近的研究表明，蛋白激酶 Aurora B 是纺锤体检查点激活的关键调节剂，而蛋白磷酸酶 PP1 则拮抗 Aurora B 并诱导检查点沉默。染色体的双定向拉伸着动粒，并在空间上将着丝粒处的 Aurora B 与其动粒底物分开，其中包括几个 PP1 相互作用蛋白（PIP）。随后这些 PIP 的去磷酸化为 PP1 向动粒的大量募集创造了停靠位点。我们提出，这种张力诱导的 PP1 靶向通过去磷酸化动粒和检查点成分（包括 Aurora B 底物）触发检查点沉默。此外，PP1 还通过拮抗 Aurora B 的着丝粒靶向，直接使与动粒相关的 Aurora B 失活，并通过拮抗 Aurora B 的着丝粒靶向来抑制检查点信号。
