Crosby S D, Puetz J J, Simburger K S, Fahrner T J, Milbrandt J
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Mol Cell Biol. 1991 Aug;11(8):3835-41. doi: 10.1128/mcb.11.8.3835-3841.1991.
We have cloned NGFI-C, a nerve growth factor-induced early-response gene which encodes a Cys2/His2 zinc finger protein. RNA blot analysis demonstrates that NGFI-C mRNA is induced within minutes of stimulation of PC12 cells by nerve growth factor and is similarly activated in brain after a Metrazol-induced seizure. The cDNA sequence predicts a protein that contains three zinc fingers which show striking homology to the DNA-binding regions of three previously reported zinc finger proteins, NGFI-A, Krox-20, and the Wilms' tumor gene product. NGFI-C binds to the previously described DNA-binding site of these three proteins, which is GCGGGGGCG. Cotransfection experiments revealed that NGFI-C strongly activates transcription from this site in mammalian cells. The isolation of another early-response gene that encodes a member of the G(C/G)G or GSG element-binding family should provide an opportunity to investigate the relative contributions of a family of transcription factors to the cell's response to changes in its environment.
我们克隆了NGFI-C,一种神经生长因子诱导的早期反应基因,它编码一种Cys2/His2锌指蛋白。RNA印迹分析表明,神经生长因子刺激PC12细胞后几分钟内,NGFI-C mRNA就被诱导产生,并且在戊四氮诱发癫痫发作后的大脑中也同样被激活。cDNA序列预测该蛋白包含三个锌指,它们与之前报道的三种锌指蛋白NGFI-A、Krox-20和威尔姆斯瘤基因产物的DNA结合区域具有显著同源性。NGFI-C与这三种蛋白先前描述的DNA结合位点GCGGGGGCG结合。共转染实验表明,NGFI-C在哺乳动物细胞中能强烈激活该位点的转录。分离出另一个编码G(C/G)G或GSG元件结合家族成员的早期反应基因,应该会为研究一类转录因子对细胞对其环境变化的反应的相对贡献提供一个机会。