Posttranslational control of Cdc25 degradation terminates Drosophila's early cell-cycle program.

Posttranslational control of Cdc25 degradation terminates Drosophila's early cell-cycle program.
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DOI:
10.1016/j.cub.2012.11.029
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发表时间:
2013-01-21
期刊:
影响因子:
9.2
通讯作者:
Wieschaus, Eric F.
Wieschaus, Eric F.
中科院分区:
生物学1区
文献类型:
--
作者:
Di Talia, Stefano;She, Richard;Blythe, Shelby A.;Lu, Xuemin;Zhang, Qi Fan;Wieschaus, Eric F.

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在大多数后生动物中,早期胚胎发育的特征是由卵子发生期间积累的母体mRNA和蛋白质控制的快速有丝分裂。这些快速分裂在囊胚中期过渡期(MBT)暂停,与基因转录的急剧增加和母体mRNA的一个子集的降解相一致。在果蝇中,细胞周期暂停是由Cdk1的抑制性磷酸化控制的,而Cdk1的抑制性磷酸化又是由激活的Cdc25磷酸酶的下调驱动的。在这里,我们表明,两个果蝇Cdc25同系物,字符串和线,不同的动力学和,与目前的模型相反,它们的下调不是由mRNA降解,但通过不同的翻译后机制控制。在合胞周期晚期,String蛋白的降解速率逐渐增加,其方式取决于核质比和DNA复制检查点。另一方面,Twine在MBT开始时通过类似String的开关机制被靶向降解,该机制由核质比控制,但不需要DNA复制检查点。我们证明了Twine降解的翻译后控制确保了适当数量的有丝分裂先于MBT。
In most metazoans, early embryonic development is characterized by rapid mitotic divisions that are controlled by maternal mRNAs and proteins that accumulate during oogenesis. These rapid divisions pause at the Mid-Blastula Transition (MBT), coinciding with a dramatic increase in gene transcription and the degradation of a subset of maternal mRNAs. In Drosophila, the cell cycle pause is controlled by inhibitory phosphorylation of Cdk1, which in turn is driven by down-regulation of the activating Cdc25 phosphatases. Here, we show that the two Drosophila Cdc25 homologues, String and Twine, differ in their dynamics and that, contrary to current models, their down-regulations are not controlled by mRNA degradation but through different post-translational mechanisms. The degradation rate of String protein gradually increases during the late syncytial cycles in a manner dependent on the nuclear-to-cytoplasmic ratio and on the DNA replication checkpoints. Twine, on the other hand, is targeted for degradation at the onset of the MBT through a switch-like mechanism controlled like String by the nuclear-to-cytoplasmic ratio, but not requiring the DNA replication checkpoints. We demonstrate that post-translational control of Twine degradation ensures that the proper number of mitoses precede the MBT.
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