Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons
Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons
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DOI：
10.1073/pnas.96.20.11317
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发表时间：
1999-09-28
影响因子：
11.1
通讯作者：
Peters, JM
中科院分区：
文献类型：
--
作者：
Gieffers, C;Peters, BH;Peters, JM
后期促进复合体/环体（APC）是一种严格调控细胞周期的泛素蛋白连接酶，在有丝分裂末期和G1期靶向细胞周期蛋白B和其他含有破坏盒的蛋白进行蛋白水解。最近的研究表明，APC在有丝分裂中的激活依赖于CDC20，而APC通过与CDC20相关蛋白CDH1的关联在G1期保持活性。本研究表明，有丝分裂激活因子CDC20是APC泛素化途径中唯一表达仅限于增殖细胞的组分，而APC和CDH1也在几种主要含有分化细胞的哺乳动物组织中表达，如成人大脑。对培养的大鼠海马神经元、小鼠和人脑切片的免疫细胞化学分析表明，APC和CDH1在有丝分裂后终末分化神经元细胞核中普遍表达。从脑中纯化的APC包含增殖细胞中已知的所有核心亚基，并与CDH1密切相关。纯化的脑ApC（CDH1）具有较高的细胞周期蛋白B泛素化活性，其依赖于有丝分裂ApC（CDC20）的活性而不是破坏盒。基于这些结果，我们提出ApC（CDH1）的功能不仅限于控制细胞周期进程，还可能包括分化细胞中尚未确定底物的泛素化。
The anaphase-promoting complex/cyclosome (APC) is a tightly cell cycle-regulated ubiquitin-protein ligase that targets cyclin B and other destruction box-containing proteins for proteolysis at the end of mitosis and in G1. Recent work has shown that activation of the APC in mitosis depends on CDC20, whereas APC is maintained active in G1 via association with the CDC20-related protein CDH1. Here we show that the mitotic activator CDC20 is the only component of the APC ubiquitination pathway whose expression is restricted to proliferating cells, whereas the APC and CDH1 are also expressed in several mammalian tissues that predominantly contain differentiated cells, such as adult brain. Immunocytochemical analyses of cultured rat hippocampal neurons and of mouse and human brain sections indicate that the APC and CDH1 are ubiquitously expressed in the nuclei of postmitotic terminally differentiated neurons. The APC purified from brain contains all core subunits known from proliferating cells and is tightly associated with CDH1. Purified brain ApC(CDH1) has a high cyclin B ubiquitination activity that depends less on the destruction box than on the activity of mitotic ApC(CDC20). On the basis of these results, we propose that the functions of ApC(CDH1) are not restricted to controlling cell-cycle progression but may include the ubiquitination of yet unidentified substrates in differentiated cells.