The E3 ubiquitin ligase skp2 regulates neural differentiation independent from the cell cycle.
The E3 ubiquitin ligase skp2 regulates neural differentiation independent from the cell cycle.
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DOI：
10.1186/1749-8104-2-27
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发表时间：
2007-12-14
影响因子：
3.6
通讯作者：
Philpott A
中科院分区：
文献类型：
--
作者：
Boix-Perales H;Horan I;Wise H;Lin HR;Chuang LC;Yew PR;Philpott A
SCFskp2复合物是一种E3泛素连接酶，已知其靶向许多细胞周期调节剂，包括细胞周期蛋白依赖性激酶抑制剂，用于蛋白水解。虽然其在细胞分裂调节中的作用已被充分记录，但在分化中的其他功能，包括在神经系统中，尚未被研究。使用非洲爪蟾作为一个模型系统，在这里，我们表明，skp2有一个额外的作用，在初级神经元的分化调节，第一个神经元分化的神经板。非洲爪蟾skp2在早期胚胎神经组织中表现出动态表达模式，skp2的缺失导致额外初级神经元的产生。相反，过度表达skp2抑制神经发生的方式依赖于其作为SCF skp2复合物的一部分的能力。此外，skp2对神经发生的抑制发生在编码NeuroD的前神经基因的上游和细胞周期退出之前。我们以前已经证明，非洲爪蟾细胞周期蛋白依赖性激酶抑制剂Xic 1是必不可少的初级神经发生在早期阶段，并在这些细胞退出细胞周期。我们发现，SCFskp2在胚胎中降解Xic1，这有助于skp2调节神经发生的能力。我们的结论是，SCFskp2复合物的功能，在控制神经元分化的细胞周期调控的作用。因此，它很好地定位为直接调节细胞增殖和细胞分化的协调因子。
The SCFskp2 complex is an E3 ubiquitin ligase that is known to target a number of cell cycle regulators, including cyclin-dependent kinase inhibitors, for proteolysis. While its role in regulation of cell division has been well documented, additional functions in differentiation, including in the nervous system, have not been investigated. Using Xenopus as a model system, here we demonstrate that skp2 has an additional role in regulation of differentiation of primary neurons, the first neurons to differentiate in the neural plate. Xenopus skp2 shows a dynamic expression pattern in early embryonic neural tissue and depletion of skp2 results in generation of extra primary neurons. In contrast, over-expression of skp2 inhibits neurogenesis in a manner dependent on its ability to act as part of the SCFskp2 complex. Moreover, inhibition of neurogenesis by skp2 occurs upstream of the proneural gene encoding NeuroD and prior to cell cycle exit. We have previously demonstrated that the Xenopus cyclin dependent kinase inhibitor Xic1 is essential for primary neurogenesis at an early stage, and before these cells exit the cell cycle. We show that SCFskp2 degrades Xic1 in embryos and this contributes to the ability of skp2 to regulate neurogenesis. We conclude that the SCFskp2 complex has functions in the control of neuronal differentiation additional to its role in cell cycle regulation. Thus, it is well placed to be a co-ordinating factor regulating both cell proliferation and cell differentiation directly.
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影响因子：
56.9
作者：
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通讯作者：
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