Dynamic Changes of Jab1 and p27kip1 Expression in Injured Rat Sciatic Nerve
Dynamic Changes of Jab1 and p27kip1 Expression in Injured Rat Sciatic Nerve
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损伤大鼠坐骨神经Jab1和p27kip1表达的动态变化
DOI：
10.1007/s12031-013-9969-8
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发表时间：
2013-09-01
影响因子：
3.1
通讯作者：
Wang, Youhua
中科院分区：
文献类型：
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作者：
Cheng, Xinghai;Zhou, Zhengming;Wang, Youhua
Jun激活域结合蛋白（Jab1）是一种多功能蛋白，参与影响信号通路、控制细胞增殖和凋亡、调节基因组不稳定性和DNA修复，是COP9信号体的关键亚基。 p27kip1 是细胞周期蛋白依赖性激酶抑制剂 Cip/Kip 家族的成员，可抑制细胞周期蛋白-CDK 复合物的酶活性，导致细胞周期停滞在 G(1)。最近的研究表明，Jab1直接与p27kip1结合并在多种人类癌症中诱导核输出和随后的降解，而Jab1和p27kip1在神经系统损伤和再生中的关联和功能仍不清楚。在此，我们建立了成年大鼠坐骨神经损伤模型，并通过Western blot研究了Jab1和p27kip1表达的动态变化。坐骨神经挤压 (SNC) 导致 Jab1 显着上调和 p27kip1 下调。此外，我们通过双重免疫荧光染色观察到Jab1在雪旺细胞（SC）中广泛表达，并且在轴突中很少共定位。此外，Jab1的表达峰值与增殖细胞核抗原（PCNA）平行，并且大量表达Jab1的SC呈PCNA阳性。免疫共沉淀和双标记获得的结果进一步表明它们在坐骨神经中的相互作用。因此，这些结果表明 Jab1 和 p27kip1 可能参与 SNC 后坐骨神经的病理生理学。
Jun activation domain-binding protein (Jab1) is a multifunctional protein that participates in affecting signaling pathway, controlling cell proliferation and apoptosis, and regulating genomic instability and DNA repair, and acts as a key subunit of COP9 signalosome. p27kip1, a member of the Cip/Kip family of cyclin-dependent kinase inhibitors, was shown to inhibit the enzymatic activity of cyclin-CDK complexes, resulting in cell-cycle arrest at G(1). Recent studies have shown that Jab1 directly binds to p27kip1 and induces nuclear export and subsequent degradation in a variety of human cancers, while the association and function of Jab1 and p27kip1 in nervous system lesion and regeneration remain unclear. Here, we performed a sciatic nerve injury model in adult rats and studied the dynamic changes of Jab1 and p27kip1 expression by Western blot. Sciatic nerve crush (SNC) resulted in a significant upregulation of Jab1 and a downregulation of p27kip1. Besides, we observed that Jab1 was expressed widely in Schwann cells (SCs) and had few co-localization in axons by double immunofluorescence staining. In addition, the peak expression of Jab1 was parallel with proliferating cell nuclear antigen (PCNA), and numerous SCs expressing Jab1 were PCNA-positive. Results obtained by co-immunoprecipitation and double labeling further showed their interaction in the sciatic nerve. Thus, these results suggested that Jab1 and p27kip1 may be involved in the pathophysiology of sciatic nerve after SNC.