Regulation of APC/CCdh1 ubiquitin ligase in differentiation of human embryonic stem cells

被引：21
|
作者：
Bar-On, Ortal [1 ,3 ]
Shapira, Ma'anit [1 ,3 ]
Skorecki, Karl [2 ,3 ]
Hershko, Avram [4 ,5 ,6 ]
Hershko, Dan D. [1 ,3 ]
机构：
[1] Technion Israel Inst Technol, Dept Surg, Haifa, Israel
[2] Technion Israel Inst Technol, Dept Nephrol, Haifa, Israel
[3] Technion Israel Inst Technol, Rambam Med Ctr, Haifa, Israel
[4] Technion Israel Inst Technol, Biochem Unit, Haifa, Israel
[5] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel
[6] Technion Israel Inst Technol, Res Inst, Haifa, Israel
来源：
CELL CYCLE | 2010年 / 9卷 / 10期
关键词：
APC/C; p27; Skp2; ubiquitin; Emi1; differentiation; ANAPHASE-PROMOTING COMPLEX; DEGRADATION; BINDING; COMPLEX/CYCLOSOME; CDC20; SKP2;
D O I：
10.4161/cc.9.10.11727
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
引用
收藏
页码：1986 / 1989
页数：4
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