Regulation of APC/C-Cdh1 and its function in neuronal survival.
Regulation of APC/C-Cdh1 and its function in neuronal survival.
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DOI：
10.1007/s12035-012-8309-2
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发表时间：
2012-12
影响因子：
5.1
通讯作者：
Almeida, Angeles
中科院分区：
文献类型：
--
作者：
Almeida, Angeles
神经元是有丝分裂后的细胞，其经历细胞周期相关蛋白的主动下调以存活。后期促进复合物/环体（APC/C），一种在增殖细胞中调节细胞周期进程的E3泛素连接酶的活性，在有丝分裂后神经元中起着相关的作用。近年来对APC/C调控的研究表明，APC/C激活辅因子Cdh 1对APC/C在神经元存活中的功能至关重要。在这里，我们回顾了APC/C活性在增殖细胞和神经元的正常调节。我们的结论是，在神经元中的APC/C-Cdh 1复合物积极下调细胞周期蛋白周期蛋白B1和糖酵解酶6-磷酸果糖-2-激酶/果糖-2，6-二磷酸酶-3的稳定性。保持这些蛋白质不稳定对于防止有丝分裂后神经元异常重新进入细胞周期和维持其降低的抗氧化状态都是至关重要的。进一步了解APC/C-Cdh 1在神经元中对这些蛋白的病理生理调节对于寻找新的神经变性治疗靶点将是重要的。
Neurons are post-mitotic cells that undergo an active downregulation of cell cycle-related proteins to survive. The activity of the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that regulates cell cycle progression in proliferating cells, plays a relevant role in post-mitotic neurons. Recent advances in the study of the regulation of APC/C have documented that the APC/C-activating cofactor, Cdh1, is essential for the function(s) of APC/C in neuronal survival. Here, we review the normal regulation of APC/C activity in proliferating cells and neurons. We conclude that in neurons the APC/C-Cdh1 complex actively downregulates the stability of the cell cycle protein cyclin B1 and the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3. Keeping these proteins destabilized is critical both for preventing the aberrant reentry of post-mitotic neurons into the cell cycle and for maintaining their reduced antioxidant status. Further understanding of the pathophysiological regulation of these proteins by APC/C-Cdh1 in neurons will be important for the search for novel therapeutic targets against neurodegeneration.
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影响因子：
64.5
作者：
Bassermann, Florian;Frescas, David;Guardavaccaro, Daniele;Busino, Luca;Peschiaroli, Angelo;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
9.2
作者：
Carroll, CW;Enquist-Newman, M;Morgan, DO
通讯作者：
Morgan, DO
影响因子：
5.3
作者：
Castro, A;Vigneron, S;Lorca, T
通讯作者：
Lorca, T
影响因子：
4.3
作者：
Berdougo, Eli;Nachury, Maxence V.;Jallepalli, Prasad V.
通讯作者：
Jallepalli, Prasad V.
影响因子：
4.3
作者：
Bar-On, Ortal;Shapira, Ma'anit;Hershko, Dan D.
通讯作者：
Hershko, Dan D.