Tikoo R, Zanazzi G, Shiffman D, Salzer J, Chao M V
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA.
J Neurosci. 2000 Jun 15;20(12):4627-34. doi: 10.1523/JNEUROSCI.20-12-04627.2000.
Schwann cell proliferation is regulated by multiple growth factors and axonal signals. However, the molecules that control growth arrest of Schwann cells are not well defined. Here we describe regulation of the cyclin-dependent kinase-2 (CDK2) protein, an enzyme that is necessary for the transition from G1 to S phase. Levels of CDK2 protein were elevated in proliferating Schwann cells cultured in serum and forskolin. However, when cells were grown with either serum-free media or at high densities, CDK2 levels declined to low levels. The decrease in CDK2 levels was associated with growth arrest of Schwann cells. The modulation of CDK2 appears to be regulated at the transcriptional level, because CDK2 mRNA levels and its promoter activity both decline during cell cycle arrest. Furthermore, analysis of the CDK2 promoter suggests that Sp1 DNA binding sites are essential for maximal activation in Schwann cells. Together, these data suggest that CDK2 may represent a significant target of developmental signals that regulate Schwann cell proliferation and that this regulation is mediated, in part, through regulation of Sp1 transcriptional activity.
施万细胞的增殖受多种生长因子和轴突信号调控。然而，控制施万细胞生长停滞的分子尚未明确界定。在此，我们描述细胞周期蛋白依赖性激酶2（CDK2）蛋白的调控情况，该酶是细胞从G1期过渡到S期所必需的。在血清和福斯高林培养的增殖施万细胞中，CDK2蛋白水平升高。然而，当细胞在无血清培养基中生长或处于高密度状态时，CDK2水平降至低水平。CDK2水平的降低与施万细胞的生长停滞相关。CDK2的调节似乎在转录水平上进行，因为在细胞周期停滞期间，CDK2 mRNA水平及其启动子活性均下降。此外，对CDK2启动子的分析表明，Sp1 DNA结合位点对于施万细胞中的最大激活至关重要。这些数据共同表明，CDK2可能是调节施万细胞增殖的发育信号的重要靶点，且这种调节部分是通过Sp1转录活性的调节介导的。
