Inhibition of cyclin-dependent kinase activity triggers neuronal differentiation of mouse neuroblastoma cells.

Inhibition of cyclin-dependent kinase activity triggers neuronal differentiation of mouse neuroblastoma cells.
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抑制细胞周期蛋白依赖性激酶活性会触发小鼠神经母细胞瘤细胞的神经元分化。

DOI:
10.1083/jcb.131.1.227
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发表时间:
1995-10
影响因子:
7.8
通讯作者:
ZANTEMA, A
ZANTEMA, A
中科院分区:
生物学1区
文献类型:
--
作者:
KRANENBURG, O;SCHARNHORST, V;VANDEREB, AJ;ZANTEMA, A

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神经分化的分子机制研究通常是利用神经母细胞瘤建立的细胞系进行的。在这项研究中,我们使用了小鼠N1E-115神经母细胞瘤细胞,这些细胞在DMSO作用下经历了神经元分化。在分化过程中,细胞周期蛋白依赖性激酶(CDK)活性下降,视网膜母细胞瘤基因产物(PRB)的磷酸化丢失,导致出现含有PRB的E2F DNA结合复合体。CDK2活性的丧失是由于CDK2丰度的降低,而CDK4活性的丧失是由于与CDK抑制物(CKI)p27KIP1的强烈结合以及CDK4磷酸化的同时丧失所致。此外,p27KIP1或pRb的过表达可诱导神经元分化,提示抑制cdk活性导致pRb磷酸化缺失是神经元分化的主要决定因素。
Studies on the molecular mechanisms underlying neuronal differentiation are frequently performed using cell lines established from neuroblastomas. In this study we have used mouse N1E-115 neuroblastoma cells that undergo neuronal differentiation in response to DMSO. During differentiation, cyclin-dependent kinase (cdk) activities decline and phosphorylation of the retinoblastoma gene product (pRb) is lost, leading to the appearance of a pRb-containing E2F DNA-binding complex. The loss of cdk2 activity is due to a decrease in cdk2 abundance whereas loss of cdk4 activity is caused by strong association with the cdk inhibitor (CKI) p27KIP1 and concurrent loss of cdk4 phosphorylation. Moreover, neuronal differentiation can be induced by overexpression of p27KIP1 or pRb, suggesting that inhibition of cdk activity leading to loss of pRb phosphorylation, is the major determinant for neuronal differentiation.
DOI: 10.1016/0092-8674(93)90110-c
发表时间: 1993-02-12
期刊: CELL
影响因子: 64.5
作者:
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通讯作者: NADALGINARD, B
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发表时间: 1994-11-04
期刊: CELL
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发表时间: 1992-08-01
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DOI: 10.1016/0006-291x(92)91714-2
发表时间: 1992-06-30
影响因子: 3.1
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