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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Atypical E2f Activity Restrains Apc/c~(ccs52a2) Function Obligatory For Endocycle Onset
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Atypical E2f Activity Restrains Apc/c~(ccs52a2) Function Obligatory For Endocycle Onset

机译：非典型E2f活性抑制了周期内发作必不可少的Apc / c〜（ccs52a2）功能

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The endocycle represents an alternative cell cycle that is activated in various developmental processes, including placental formation, Drosophila oogenesis, and leaf development. In endocycling cells, mitotic cell cycle exit is followed by successive doublings of the DNA content, resulting in polyploidy. The timing of endocycle onset is crucial for correct development, because polyploidization is linked with cessation of cell division and initiation of terminal differentiation. The anaphase-promoting complex/cyclosome (APC/C) activator genes CDH1, FZR, and CCS52 are known to promote endocycle onset in human, Drosophila, and Medicago species cells, respectively; however, the genetic pathways governing development-dependent APC/C~(CDH1/FZR/CCS52) activity remain unknown. We report that the atypical E2F transcription factor E2Fe/DEL1 controls the expression of the CDH1/FZR orthologous CCS52A2 gene from Arabidopsis thaliana. E2Fe/DEL1 misregulation resulted in untimely CCS52A2 transcription, affecting the timing of endocycle onset. Correspondingly, ectopic CCS52A2 expression drove cells into the endocycle prematurely. Dynamic simulation illustrated that E2Fe/DEL1 accounted for the onset of the endocycle by regulating the temporal expression of CCS52A2 during the cell cycle in a development-dependent manner. Analogously, the atypical mammalian E2F7 protein was associated with the promoter of the APC/C-activating CDH1 gene, indicating that the transcriptional control of APC/C activator genes by atypical E2Fs might be evolu-tionarily conserved.
机译：内循环代表了一个可替代的细胞周期，该周期在各种发育过程中被激活，包括胎盘形成，果蝇卵发生和叶片发育。在内吞细胞中，有丝分裂细胞周期退出后，DNA含量连续翻倍，从而形成多倍体。内循环发生的时机对于正确发育至关重要，因为多倍体化与细胞分裂的停止和终末分化的开始有关。已知后期促进复合物/环体（APC / C）激活基因CDH1，FZR和CCS52分别促进人，果蝇和苜蓿物种细胞中的内循环发作。然而，控制发育依赖的APC / C〜（CDH1 / FZR / CCS52）活性的遗传途径仍然未知。我们报告非典型E2F转录因子E2Fe / DEL1控制拟南芥CDH1 / FZR直系同源CCS52A2基因的表达。 E2Fe / DEL1的失调导致CCS52A2的转录不及时，从而影响了内循环发作的时机。相应地，异位CCS52A2表达将细胞过早地带入了细胞周期。动态模拟表明，E2Fe / DEL1通过以依赖于发育的方式调节细胞周期期间CCS52A2的时间表达来解释内循环的发生。类似地，非典型哺乳动物E2F7蛋白与APC / C激活CDH1基因的启动子相关，这表明非典型E2F对APC / C激活基因的转录控制可能在进化上是保守的。

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