c-Jun Expression, activation and function in neural cell death, inflammation and repair
c-Jun Expression, activation and function in neural cell death, inflammation and repair
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DOI：
10.1111/j.1471-4159.2008.05684.x
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发表时间：
2008-11-01
影响因子：
4.7
通讯作者：
Raivich, Gennadij
中科院分区：
文献类型：
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作者：
Raivich, Gennadij
C-jun的上调在发育中的成人神经系统以及受损的神经系统中都是常见的事件，它是大脑功能转录调控的模型。使用基因缺失、显性负性异构体的靶向表达和药物抑制剂的体内功能研究都表明，c-jun作用具有三个方面的作用，即控制神经细胞的死亡和退化，在胶质增生和炎症中，以及在可塑性和修复中。在体外，结构和分子研究揭示了几个非重叠的激活级联反应，包括N端丝氨酸63和73(Ser63，Ser73)和苏氨酸91和93(Thr91，Thr93)残基的磷酸化，Thr239处的去磷酸化，P300介导的近C末端区域(Lys268，Lys271，Lys 273)的赖氨酸乙酰化，以及Jun N端丝氨酸/苏氨酸激酶家族Jun独立的活性，调节不同和不同的细胞反应。更好地了解这些在体内的非重叠作用可以极大地提高药物的潜力，以改善创伤、新生儿脑病和中风以及神经退行性疾病的神经预后。
Up-regulation of c-Jun is a common event in the developing, adult as well as in injured nervous system that serves as a model of transcriptional control of brain function. Functional studies employing in vivo strategies using gene deletion, targeted expression of dominant negative isoforms and pharmacological inhibitors all suggest a three pronged role of c-Jun action, exercising control over neural cell death and degeneration, in gliosis and inflammation as well as in plasticity and repair. In vitro, structural and molecular studies reveal several non-overlapping activation cascades via N-terminal c-Jun phosphorylation at serine 63 and 73 (Ser63, Ser73), and threonine 91 and 93 (Thr91, Thr93) residues, the dephosphorylation at Thr239, the p300-mediated lysine acetylation of the near C-terminal region (Lys268, Lys271, Lys 273), as well as the Jun-independent activities of the Jun N-terminal family of serine/threonine kinases, that regulate the different and disparate cellular responses. A better understanding of these non-overlapping roles in vivo could considerably increase the potential of pharmacological agents to improve neurological outcome following trauma, neonatal encephalopathy and stroke, as well as in neurodegenerative disease.