Lee M H, Nikolic M, Baptista C A, Lai E, Tsai L H, Massagué J
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3259-63. doi: 10.1073/pnas.93.8.3259.
Cell cycle withdrawal in postmitotic cells involves cyclin-dependent kinase (Cdk) inhibitors that repress cell cycle Cdk activity. During mouse neurogenesis, cortical postmitotic neurons are shown here to accumulate high levels of the p27 Cdk inhibitor compared with their progenitor neuroblasts. Elevated p27 levels in staged embryo brain extracts correlate with p27 binding to Cdk2, and Cdk inactivation. Yet, Cdk5, which is associated with the noncyclin activator p35 in neurons, remains active in the presence of high p27 levels. Both in vitro and in vivo, p27 and related inhibitors can recognize a cyclin D-Cdk5 complex but not a p35-Cdk5 complex. The results indicate that the choice of activator determines the susceptibility of Cdk5 to p27 and related Cdk inhibitors, and thus its ability to act in postmitotic cells.
有丝分裂后细胞中的细胞周期停滞涉及抑制细胞周期依赖性激酶（Cdk）活性的细胞周期蛋白依赖性激酶抑制剂。在小鼠神经发生过程中，与祖神经母细胞相比，皮质有丝分裂后神经元显示出高水平的p27 Cdk抑制剂积累。分期胚胎脑提取物中升高的p27水平与p27与Cdk2的结合以及Cdk失活相关。然而，在神经元中与非细胞周期蛋白激活剂p35相关的Cdk5在高p27水平存在时仍保持活性。在体外和体内，p27和相关抑制剂都能识别细胞周期蛋白D-Cdk5复合物，但不能识别p35-Cdk5复合物。结果表明，激活剂的选择决定了Cdk5对p27和相关Cdk抑制剂的敏感性，从而决定了其在有丝分裂后细胞中的作用能力。
