The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis.
The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis.
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DOI：
10.1186/1749-8104-5-1
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发表时间：
2010-01-04
影响因子：
3.6
通讯作者：
Philpott A
中科院分区：
文献类型：
--
作者：
Almeida AD;Wise HM;Hindley CJ;Slevin MK;Hartley RS;Philpott A
神经嵴是脊椎动物外胚层中神经板边界处出现的独特细胞群，之后它们在整个胚胎中广泛迁移，产生广泛的衍生物。许多参与神经嵴发育的蛋白质具有动态表达模式，并且越来越清楚的是，泛素介导的蛋白质降解是造成这一点的部分原因。在这里，我们证明了一个新的作用，F-盒蛋白Cdc 4/Fbxw 7在神经嵴的发展。非洲爪蟾Cdc 4基因有两种亚型，分别命名为xCdc 4 α和xCdc 4 β。这些与脊椎动物Cdc 4同源物高度保守，并且爪蟾蛋白在降解细胞周期蛋白E（一种已建立的脊椎动物Cdc 4靶点）的能力方面在功能上等同。阻断xCdc 4功能在早期阶段特异性地抑制神经嵴发育，在c-Myc、Snail 2和Snail表达之前。我们证明，Cdc 4，泛素E3连接酶亚基先前确定为主要针对细胞周期调节蛋白水解，有额外的作用，在控制神经嵴的形成。因此，我们确定Cdc 4作为一种蛋白质，在控制细胞增殖和分化中具有可分离但互补的功能。
The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this. Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4α and xCdc4β. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail. We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation.
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影响因子：
64.5
作者：
Feldman, RMR;Correll, CC;Deshaies, RJ
通讯作者：
Deshaies, RJ
影响因子：
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Hao, Bing;Oehlmann, Stephanie;Pavletich, Nikola P.
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Nateri, AS;Riera-Sans, L;Behrens, A
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影响因子：
3.6
作者：
Boix-Perales H;Horan I;Wise H;Lin HR;Chuang LC;Yew PR;Philpott A
通讯作者：
Philpott A