Regulation of APC/CCdh1 ubiquitin ligase in differentiation of human embryonic stem cells
Regulation of APC/CCdh1 ubiquitin ligase in differentiation of human embryonic stem cells
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DOI：
10.4161/cc.9.10.11727
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发表时间：
2010-05-15
期刊：
影响因子：
4.3
通讯作者：
Hershko, Dan D.
中科院分区：
文献类型：
--
作者：
Bar-On, Ortal;Shapira, Ma'anit;Hershko, Dan D.
我们最近发现，Skp2水平在未分化的人胚胎干细胞中很高，但在诱导分化后迅速下降，从而导致p27的积累。发现Skp2水平的变化主要是由其降解速率引起的。我们发现APC/C-Cdh1（靶向Skp2降解的泛素连接酶）的活性在人胚胎干细胞分化过程中显著增加。APC/C-Cdh1在未分化的胚胎干细胞中存在但不活跃，并在分化状态下变得活跃。APC/C-Cdh1活性的上升与分化似乎至少部分是由于其抑制剂Emi1水平的急剧下降。此外，蛋白激酶活性似乎也有助于抑制未分化干细胞中APC/C-Cdh1活性，可能是通过抑制Cdh1的磷酸化。
We have recently shown that Skp2 levels are high in undifferentiated human embryonic stem cells, but decline rapidly following induction of differentiation, thereby leading to accumulation of p27. Changes in Skp2 levels were found to be caused mainly by its rate of degradation. Here we show that the activity of APC/C-Cdh1, the ubiquitin ligase that targets Skp2 for degradation, increases markedly during the differentiation process of human embryonic stem cells. APC/C-Cdh1 is present but inactive in undifferentiated embryonic stem cells and becomes active in the differentiated state. The rise in APC/C-Cdh1 activity with differentiation appears to be due, at least in part, to a dramatic decline in the levels of its inhibitor Emi1. In addition, protein kinase activity also appears to contribute to the suppression of APC/C-Cdh1 activity in undifferentiated stem cells, possibly by inhibitory phosphorylation of Cdh1.