Adaptation to the spindle checkpoint is regulated by the interplay between Cdc28/Clbs and PP2ACdc55.
Adaptation to the spindle checkpoint is regulated by the interplay between Cdc28/Clbs and PP2ACdc55.
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DOI：
10.1083/jcb.201303033
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发表时间：
2013-09-02
期刊：
影响因子：
--
通讯作者：
Ciliberto A
中科院分区：
文献类型：
--
作者：
Vernieri C;Chiroli E;Francia V;Gross F;Ciliberto A
PP2ACdc55使APC/CCdc20去磷酸化以防止后期，这一效应可被CDc28/Clbs抵消以允许纺锤体检查点适应。纺锤体检查点在中期阻止细胞，直到所有的染色体都正确地连接到染色体分离机制上。此后，后期促进复合体(APC/C)被激活，染色体可以发生分离。作为对检查点激活的反应，细胞在有丝分裂中停留数小时，但不是无限期的。最终，它们适应检查点并沿着细胞周期前进。在酵母中，适应需要APC/C的磷酸化。在这里，我们证明了蛋白磷酸酶PP2ACdc55使APC/C去磷酸化，从而抵消了有丝分裂激酶CDC28的活性。我们还观察到，CDc28的关键调节因子，有丝分裂周期蛋白Clb2，在细胞适应之前增加，然后在适应时突然降解。适应是高度不同步的，需要几个小时的时间。我们的数据表明，PP2ACdc55和APC/CCdc20之间存在一个控制APC/CCdc20活动的双负环(即正反馈环)。在Clb2开始降解后，该电路可以保证持续的APC/CCdc20活性。
PP2ACdc55 dephosphorylates APC/CCdc20 to prevent anaphase, an effect that is counteracted by Cdc28/Clbs to allow for spindle checkpoint adaptation. The spindle checkpoint arrests cells in metaphase until all chromosomes are properly attached to the chromosome segregation machinery. Thereafter, the anaphase promoting complex (APC/C) is activated and chromosome segregation can take place. Cells remain arrested in mitosis for hours in response to checkpoint activation, but not indefinitely. Eventually, they adapt to the checkpoint and proceed along the cell cycle. In yeast, adaptation requires the phosphorylation of APC/C. Here, we show that the protein phosphatase PP2ACdc55 dephosphorylates APC/C, thereby counteracting the activity of the mitotic kinase Cdc28. We also observe that the key regulator of Cdc28, the mitotic cyclin Clb2, increases before cells adapt and is then abruptly degraded at adaptation. Adaptation is highly asynchronous and takes place over a range of several hours. Our data suggest the presence of a double negative loop between PP2ACdc55 and APC/CCdc20 (i.e., a positive feedback loop) that controls APC/CCdc20 activity. The circuit could guarantee sustained APC/CCdc20 activity after Clb2 starts to be degraded.
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DOI：
10.1083/jcb.201301130
发表时间：
2013-04-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Primorac I;Musacchio A
通讯作者：
Musacchio A
影响因子：
9.2
作者：
Mariani, Luca;Chiroli, Elena;Ciliberto, Andrea
通讯作者：
Ciliberto, Andrea
影响因子：
64.5
作者：
Queralt, Ethel;Lehane, Chris;Uhlmann, Frank
通讯作者：
Uhlmann, Frank
影响因子：
56.9
作者：
Palframan, William J.;Meehl, Janet B.;Murray, Andrew W.
通讯作者：
Murray, Andrew W.
影响因子：
11.4
作者：
Liang, Hongqing;Lim, Hong Hwa;Surana, Uttam
通讯作者：
Surana, Uttam