NRP/B, a novel nuclear matrix protein, associates with p110(RB) and is involved in neuronal differentiation.

NRP/B, a novel nuclear matrix protein, associates with p110(RB) and is involved in neuronal differentiation.
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DOI:
10.1083/jcb.141.3.553
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发表时间:
1998-05-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Avraham S
Avraham S
中科院分区:
其他
文献类型:
--
作者:
Kim TA;Lim J;Ota S;Raja S;Rogers R;Rivnay B;Avraham H;Avraham S

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核基质被定义为细胞核的不溶性框架,通过与细胞骨架的中间细丝的连接,涉及基因表达、细胞周期和核结构完整性的调节。我们发现了一种新的核基质蛋白NRP/B(核限制性蛋白/脑),它包含两个主要的结构元件:预测NH2末端的BTB结构域样结构,以及预测cooh末端结构域的kelch基序。NRP/B mRNA (5.5 kb)主要表达于人胎儿和成人大脑,少量表达于肾脏和胰腺。在小鼠胚胎发生过程中,神经系统中NRP/B mRNA的表达上调。NRP/B蛋白在大鼠海马原代神经元中表达,而在原代星形胶质细胞中不表达。在小鼠神经2A和人SH-SY5Y神经母细胞瘤细胞分化过程中,NRP/B表达上调。NRP/B在这些细胞中的过度表达增强了神经元过程的形成。反义NRP/B寡脱氧核苷酸处理可抑制大鼠海马原代神经元的神经突发育和PC-12细胞神经元分化过程中神经元突的形成。由于发现低磷酸化形式的视网膜母细胞瘤蛋白(p110RB)与核基质相关,并且p110RB的过表达诱导神经元分化,我们研究了NRP/B是否与p110RB相关。体内和体外实验均表明,在视黄酸诱导的SH-SY5Y神经母细胞瘤细胞分化过程中,NRP/B可被磷酸化并与功能活跃的低磷酸化形式的p110RB结合。我们的研究表明,NRP/B是一种新的核基质蛋白,特异表达于原代神经元中,与p110RB相互作用,参与神经元过程形成的调控。
The nuclear matrix is defined as the insoluble framework of the nucleus and has been implicated in the regulation of gene expression, the cell cycle, and nuclear structural integrity via linkage to intermediate filaments of the cytoskeleton. We have discovered a novel nuclear matrix protein, NRP/B (nuclear restricted protein/brain), which contains two major structural elements: a BTB domain–like structure in the predicted NH2 terminus, and a “kelch motif” in the predicted COOH-terminal domain. NRP/B mRNA (5.5 kb) is predominantly expressed in human fetal and adult brain with minor expression in kidney and pancreas. During mouse embryogenesis, NRP/B mRNA expression is upregulated in the nervous system. The NRP/B protein is expressed in rat primary hippocampal neurons, but not in primary astrocytes. NRP/B expression was upregulated during the differentiation of murine Neuro 2A and human SH-SY5Y neuroblastoma cells. Overexpression of NRP/B in these cells augmented neuronal process formation. Treatment with antisense NRP/B oligodeoxynucleotides inhibited the neurite development of rat primary hippocampal neurons as well as the neuronal process formation during neuronal differentiation of PC-12 cells. Since the hypophosphorylated form of retinoblastoma protein (p110RB) is found to be associated with the nuclear matrix and overexpression of p110RB induces neuronal differentiation, we investigated whether NRP/B is associated with p110RB. Both in vivo and in vitro experiments demonstrate that NRP/B can be phosphorylated and can bind to the functionally active hypophosphorylated form of the p110RB during neuronal differentiation of SH-SY5Y neuroblastoma cells induced by retinoic acid. Our studies indicate that NRP/B is a novel nuclear matrix protein, specifically expressed in primary neurons, that interacts with p110RB and participates in the regulation of neuronal process formation.
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DOI: 10.1006/excr.1994.1044
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影响因子: 3.7
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