KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint.
KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint.
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DOI：
10.1016/j.cub.2011.04.011
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发表时间：
2011-06-07
期刊：
影响因子：
9.2
通讯作者：
Funabiki, Hironori
中科院分区：
文献类型：
--
作者：
Rosenberg, Jessica S.;Cross, Frederick R.;Funabiki, Hironori
纺锤体组装检查点（SAC）延迟后期开始，直到着丝粒完成双向微管附着。虽然几种着丝粒和动粒激酶，包括极光B，调节着丝粒微管附着和/或SAC激活，但将双向附着转化为SAC沉默的分子机制仍不清楚。采用一种方法来快速诱导芽殖酵母中的精确基因替换，我们在这里表明，蛋白磷酸酶1（PP 1/Glc 7）的结合到进化上保守的RVSF基序的动粒蛋白Spc 105（KNL 1/Blinkin/CASC 5）是必不可少的生存能力沉默的SAC，而它起着辅助的物理染色体分离的非必要作用。虽然极光B可能会抑制这种结合，持续的PP 1-Spc 105相互作用不影响染色体分离，是不足以沉默的SAC在微管的情况下，表明这种相互作用的动态调节是不确定的。然而，PP 1靶向动粒的量必须微调，因为没有或一个额外的PP 1拷贝的Spc 105的招聘是有害的，说明了PP 1靶向动粒的重要影响。我们建议，PP 1-Spc 105相互作用，使当地的动态磷酸化和去磷酸化的动粒耦合微管附着和SAC沉默的调节。
The spindle assembly checkpoint (SAC) delays anaphase onset until kinetochores accomplish bioriented microtubule attachments. While several centromeric and kinetochore kinases, including Aurora B, regulate kinetochore-microtubule attachment and/or SAC activation, the molecular mechanism that translates bioriented attachment into SAC silencing remains unclear. Employing a method to rapidly induce exact gene replacement in budding yeast, we show here that the binding of protein phosphatase 1 (PP1/Glc7) to the evolutionarily conserved RVSF motif of the kinetochore protein Spc105 (KNL1/Blinkin/CASC5) is essential for viability by silencing the SAC, while it plays an auxiliary nonessential role for physical chromosome segregation. Although Aurora B may inhibit this binding, persistent PP1-Spc105 interaction does not affect chromosome segregation and is insufficient to silence the SAC in the absence of microtubules, indicating that dynamic regulation of this interaction is dispensable. However, the amount of PP1 targeted to kinetochores must be finely tuned, since recruitment of either none or one extra copy of PP1 to Spc105 is detrimental, illustrating the vital impact of targeting an exiguous fraction of PP1 to the kinetochore. We propose that the PP1-Spc105 interaction enables local regulation of dynamic phosphorylation and dephosphorylation at the kinetochore to couple microtubule attachment and SAC silencing.
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影响因子：
7.5
作者：
Kelly AE;Funabiki H
通讯作者：
Funabiki H
DOI：
10.1016/j.cub.2009.06.043
发表时间：
2009-07-28
期刊：
Current biology : CB
影响因子：
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作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Hardwick, Kevin G.