Mechanism and regulation of Cdc25/Twine protein destruction in embryonic cell-cycle remodeling.
Mechanism and regulation of Cdc25/Twine protein destruction in embryonic cell-cycle remodeling.
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DOI：
10.1016/j.cub.2012.11.036
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发表时间：
2013-01-21
期刊：
影响因子：
9.2
通讯作者：
O'Farrell, Patrick H.
中科院分区：
文献类型：
--
作者：
Farrell, Jeffrey A.;O'Farrell, Patrick H.
在果蝇胚胎中，囊胚中期转变(MBT)在第14个间期极大地重塑了细胞周期。在MBT之前，每个周期只由一个较短的S期和有丝分裂组成。在MBT阶段，S阶段由于晚期复制的开始而显著延长，并引入了G2阶段。这两个变化都为原肠形成奠定了基础，并需要下调CDC25磷酸酶，此前人们认为CDC25磷酸酶在MBT上的转录被消除了。RNAi过早移除CDC25转录本并不影响进展为MBT。相反，一种针对CDC25亚型Twin的抗体表明，Twin蛋白在MBT之前是丰富和稳定的，当它被破坏并迅速消除时。Twin的前MBT水平的持续足以防止细胞周期放缓。缠绕蛋白的破坏由核质比决定，并取决于MBT合子转录的激活，包括TRIBRS基因的表达，该基因的活性足以引发Twin破坏，并需要迅速消失。我们认为，发育调节的Twin蛋白的破坏是导致MBT细胞周期变化的关键开关，包括增加G2期和启动后期复制。此外，我们还表明，这种破坏是由TRIBBRS和其他未知基因的合子转录的核质比依赖的启动触发的。
In Drosophila embryos, the mid-blastula transition (MBT) dramatically remodels the cell cycle during the fourteenth interphase. Before the MBT, each cycle is composed of only a short S phase and mitosis. At the MBT, S phase is dramatically lengthened by the onset of late replication, and a G2 phase is introduced. Both changes set the stage for gastrulation and require downregulation of Cdc25 phosphatase, which was previously attributed to the elimination of its transcripts at the MBT. Premature removal of Cdc25 transcripts by RNAi did not affect progression to the MBT. Instead, an antibody against the Cdc25 isoform, Twine, showed that Twine protein was abundant and stable until the MBT, when it was destabilized and rapidly eliminated. Persistence of pre-MBT levels of Twine was sufficient to prevent cell cycle slowing. Twine protein destruction was timed by the nucleo-cytoplasmic ratio and depended on the activation of zygotic transcription at the MBT, including expression of the gene tribbles, whose activity was sufficient to trigger Twine destruction and was required for prompt Twine disappearance. We propose that the developmentally regulated destruction of Twine protein is a critical switch that contributes to the cell cycle change at the MBT, including the addition of a G2 phase and onset of late replication. Moreover, we show that this destruction is triggered by the nucleo-cytoplasmic ratio-dependent onset of zygotic transcription of tribbles and other unknown genes.
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