Shim Ki Shuk, Rosner Margit, Freilinger Angelika, Lubec Gert, Hengstschläger Markus
Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Exp Cell Res. 2006 Jul 15;312(12):2264-78. doi: 10.1016/j.yexcr.2006.03.018. Epub 2006 Apr 24.
Bach1 and Bach2 are evolutionarily related members of the BTB-basic region leucine zipper transcription factor family. We found that Bach2 downregulates cell proliferation of N1E-115 cells and negatively affects their potential to differentiate. Nuclear localization of the cyclin-dependent kinase inhibitor p21 is known to arrest cell cycle progression, and cytoplasmic p21 has been shown to promote neuronal differentiation of N1E-115 cells. We found that ectopic Bach2 causes upregulation of p21 expression in the nucleus and in the cytoplasm in undifferentiated N1E-115 cells. In differentiated cells, Bach2 specifically triggers upregulation of cytoplasmic p21. Our data suggest that Bach2 expression could represent a switch during the process of neuronal differentiation. Bach2 is not expressed in neuronal precursor cells. It would have negative effects on proliferation and differentiation of these cells. In differentiated neuronal cells Bach2 expression is upregulated, which could allow Bach2 to function as a gatekeeper of the differentiated status.
Bach1和Bach2是BTB-碱性区域亮氨酸拉链转录因子家族中具有进化相关性的成员。我们发现Bach2可下调N1E-115细胞的增殖,并对其分化潜能产生负面影响。已知细胞周期蛋白依赖性激酶抑制剂p21的核定位可阻止细胞周期进程,并且已证明细胞质中的p21可促进N1E-115细胞的神经元分化。我们发现异位表达的Bach2会导致未分化的N1E-115细胞核内和细胞质中p21表达上调。在分化细胞中,Bach2特异性地触发细胞质中p21的上调。我们的数据表明,Bach2的表达可能代表神经元分化过程中的一个开关。Bach2在神经元前体细胞中不表达。它会对这些细胞的增殖和分化产生负面影响。在分化的神经元细胞中,Bach2的表达上调,这可能使Bach2作为分化状态的守门人发挥作用。