Cdk5 and the non-catalytic arrest of the neuronal cell cycle.

Cdk5 and the non-catalytic arrest of the neuronal cell cycle.
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DOI:
10.4161/cc.7.22.7045
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发表时间:
2008-11-15
期刊:
Cell cycle (Georgetown, Tex.)
影响因子:
--
通讯作者:
Herrup K
Herrup K
中科院分区:
其他
文献类型:
--
作者:
Zhang J;Herrup K

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细胞周期蛋白依赖性激酶5 (Cdk5)是一种非传统的Cdk,主要活跃于有丝分裂后神经元中。Cdk5的一个重要核心功能涉及调节胚胎有丝分裂后神经元的迁移和成熟。这些发育作用依赖于它的激酶活性。最初,很少有证据表明Cdk5在正常细胞周期调节中起作用。然而,我们实验室最近的数据表明,Cdk5在正常的有丝分裂后神经元和神经元细胞系中作为细胞周期抑制因子起着至关重要的作用。它以激酶独立的方式完成这个基础。Cdk5通常存在于细胞核和细胞质中,但在阿尔茨海默病患者的大脑中,它存在于神经元细胞核中,有死亡的风险。亚细胞位置的转移伴随着细胞周期的重新进入和神经元的死亡。Cdk5的这种“新”功能在设计用于治疗神经退行性疾病的Cdk5导向药物时提出了警告。
Cyclin-dependent kinase 5 (Cdk5) is a nontraditional Cdk that is primarily active in postmitotic neurons. An important core function of Cdk5 involves regulating the migration and maturation of embryonic post-mitotic neurons. These developmental roles are dependent on its kinase activity. Initially, there was little evidence indicating a role for Cdk5 in normal cell cycle regulation. Recent data from our lab, however, suggest that Cdk5 plays a crucial role as a cell cycle suppressor in normal post-mitotic neurons and neuronal cell lines. It performs this foundation in a kinase independent manner. Cdk5 normally found in both nucleus and cytoplasm, but it exits the nucleus in neurons risk to death in an AD patient’s brain. The shift in sub-cellular location is accompanied by cell cycle re-entry and neuronal death. This “new” function of Cdk5 raises cautions in the design of Cdk5-directed drugs for the therapy of neurodegenerative diseases.
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