How APC/C-Cdc20 changes its substrate specificity in mitosis.

How APC/C-Cdc20 changes its substrate specificity in mitosis.
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DOI:
10.1038/ncb2165
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发表时间:
2011-03
影响因子:
21.3
通讯作者:
Pines J
Pines J
中科院分区:
生物学1区
文献类型:
--
作者:
Izawa D;Pines J

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通过有丝分裂的进展需要在正确的时间降解正确的蛋白质。一种泛素连接酶,后期促进复合物或环体(APC-C)通过在整个有丝分裂过程中改变其底物特异性来靶向大多数关键的有丝分裂调节剂。纺锤体组装检查点(SAC)作用于APC-C共激活剂Cdc 20,以阻止中期底物的降解,例如:细胞周期蛋白B1和securin,但不是其他,例如:细胞周期蛋白A这是如何实现的尚不清楚。在这里,我们表明Cdc 20结合到APC-C上的不同位点,这取决于SAC。当SAC被满足时,Cdc 20需要APC 3和APC 8来绑定并激活APC-C,但是当SAC被激活时,仅需要APC 8。此外,APC 10对Cyclin B1和securin的破坏至关重要,但对Cyclin A的破坏不重要。我们得出结论,SAC导致Cdc 20结合到APC-C上的不同位点,这改变了APC-C底物特异性。
Progress through mitosis requires that the right protein be degraded at the right time. One ubiquitin ligase, the Anaphase Promoting Complex or Cyclosome (APC-C) targets most of the crucial mitotic regulators by changing its substrate specificity throughout mitosis. The Spindle Assembly Checkpoint (SAC) acts on the APC-C co-activator, Cdc20 to block the degradation of metaphase substrates, e.g.: Cyclin B1 and securin, but not others, e.g.: Cyclin A. How this is achieved is unclear. Here we show that Cdc20 binds to different sites on the APC-C depending on the SAC. Cdc20 requires APC3 and APC8 to bind and activate the APC-C when the SAC is satisfied, but only requires APC8 when the SAC is active. Moreover, APC10 is crucial for Cyclin B1 and securin but not Cyclin A destruction. We conclude that the SAC causes Cdc20 to bind to different sites on the APC-C and this alters APC-C substrate specificity.
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