A double-assurance mechanism controls cell cycle exit upon terminal differentiation in Drosophila
A double-assurance mechanism controls cell cycle exit upon terminal differentiation in Drosophila
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DOI：
10.1016/j.devcel.2007.02.020
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发表时间：
2007-04-01
影响因子：
11.8
通讯作者：
Edgar, Bruce A.
中科院分区：
文献类型：
--
作者：
Buttitta, Laura A.;Katzaroff, Alexia J.;Edgar, Bruce A.
末端分化通常伴随着细胞周期的永久退出，但目前尚不清楚分化组织中细胞增殖是如何被阻止的。我们研究了果蝇翅膀和眼睛的细胞周期退出过程，发现在终末分化的细胞中，通过同时激活E2F1和Cyclin E/CDK2或Cyclin D/CDK4，可以阻止甚至逆转细胞周期退出。需要同时加强E2F和Cyclin/CDK的活性才能绕过Exit，因为E2F和Cyclin E/CDK2之间的反馈在细胞分化后被抑制，确保了细胞周期退出的健壮。在一些分化细胞类型(如神经元)中，包括视网膜母细胞瘤同源基因RBF和p27同源基因Dacapo在内的已知抑制剂有助于平行抑制E2F和Cyclin E/CDK2。然而，在其他类型的细胞(如翼上皮细胞)中，未知的机制同时抑制E2F和Cyclin/CDK的活性，以强制在终末分化时永久退出细胞周期。
Terminal differentiation is often coupled with permanent exit from the cell cycle, yet it is unclear how cell proliferation is blocked in differentiated tissues. We examined the process of cell cycle exit in Drosophila wings and eyes and discovered that cell cycle exit can be prevented or even reversed in terminally differentiating cells by the simultaneous activation of E2F1 and either Cyclin E/Cdk2 or Cyclin D/Cdk4. Enforcing both E2F and Cyclin/Cdk activities is required to bypass exit because feedback between E2F and Cyclin E/Cdk2 is inhibited after cells differentiate, ensuring that cell cycle exit is robust. In some differentiating cell types (e.g., neurons), known inhibitors including the retinoblastoma homolog Rbf and the p27 homolog Dacapo contribute to parallel repression of E2F and Cyclin E/Cdk2. In other cell types, however (e.g., wing epithelial cells), unknown mechanisms inhibit E2F and Cyclin/Cdk activity in parallel to enforce permanent cell cycle exit upon terminal differentiation.