Kranenburg O, Scharnhorst V, Van der Eb A J, Zantema A
Sylvius Laboratory, Department of Molecular Carcinogenesis, Leiden University, The Netherlands.
J Cell Biol. 1995 Oct;131(1):227-34. doi: 10.1083/jcb.131.1.227.
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.
关于神经元分化潜在分子机制的研究，常常使用源自神经母细胞瘤建立的细胞系来进行。在本研究中，我们使用了小鼠N1E - 115神经母细胞瘤细胞，这些细胞在二甲基亚砜（DMSO）作用下会发生神经元分化。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）的磷酸化消失，导致出现一种含pRb的E2F DNA结合复合物。cdk2活性的丧失是由于cdk2丰度降低，而cdk4活性的丧失是由于与细胞周期蛋白依赖性激酶抑制剂（CKI）p27KIP1强烈结合以及cdk4磷酸化同时丧失所致。此外，p27KIP1或pRb的过表达可诱导神经元分化，这表明抑制cdk活性导致pRb磷酸化丧失，是神经元分化的主要决定因素。
