Yajima S, Lammers C H, Lee S H, Hara Y, Mizuno K, Mouradian M M
Genetic Pharmacology Unit, Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, Bethesda, Maryland 20892, USA.
J Neurosci. 1997 Nov 15;17(22):8657-66. doi: 10.1523/JNEUROSCI.17-22-08657.1997.
The potent neurotrophic factor glial cell-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor-beta (TGF-beta) superfamily of proteins. We report a transcription factor that is the first nuclear protein known to be induced by GDNF, thus designated murine GDNF inducible factor (mGIF). The cDNA was cloned in the course of investigating transcription factors that bind to Sp1 consensus sequences, using the in situ filter detection method, and it was found to encode a protein having the same C2-H2 zinc finger motif as Sp1. Sequence analysis indicated that mGIF is homologous to the human TGF-beta inducible early gene (TIEG) and human early growth response gene-alpha (EGR-alpha). mGIF is widely distributed in the adult mouse with high mRNA levels in kidney, lung, brain, liver, heart, and testis. In the adult brain, mGIF is abundantly expressed in hippocampus, cerebral cortex, cerebellum, and amygdala with lower amounts in striatum, nucleus accumbens, olfactory tubercle, thalamus, and substantia nigra. During development, mGIF mRNA also has a wide distribution, including in cerebral cortex, cerebellar primordium, kidney, intestine, liver, and lung. GDNF induces the expression of mGIF rapidly and transiently both in a neuroblastoma cell line and in primary cultures of rat embryonic cortical neurons. Co-transfection of the Drosophila SL2 cells using mGIF expression plasmid and reporter constructs having Sp1 binding sites indicated that mGIF represses transcription from a TATA-containing as well as from a TATA-less promoter. These observations suggest that the zinc finger transcription factor mGIF could be important in mediating some of the biological effects of GDNF.
强效神经营养因子胶质细胞源性神经营养因子（GDNF）是转化生长因子-β（TGF-β）超家族蛋白中的一个远亲成员。我们报告了一种转录因子，它是已知的首个由GDNF诱导的核蛋白，因此被命名为小鼠GDNF诱导因子（mGIF）。在使用原位滤膜检测方法研究与Sp1共有序列结合的转录因子的过程中，该cDNA被克隆出来，并且发现它编码一种与Sp1具有相同C2-H2锌指基序的蛋白质。序列分析表明，mGIF与人TGF-β诱导早期基因（TIEG）和人早期生长反应基因-α（EGR-α）同源。mGIF在成年小鼠中广泛分布，在肾脏、肺、脑、肝脏、心脏和睾丸中mRNA水平较高。在成年大脑中，mGIF在海马体、大脑皮层、小脑和杏仁核中大量表达，在纹状体、伏隔核、嗅结节、丘脑和黑质中的表达量较低。在发育过程中，mGIF mRNA也有广泛分布，包括在大脑皮层、小脑原基、肾脏、肠道、肝脏和肺中。GDNF在神经母细胞瘤细胞系和大鼠胚胎皮质神经元原代培养物中都能快速且短暂地诱导mGIF的表达。使用mGIF表达质粒和具有Sp1结合位点的报告构建体对果蝇SL2细胞进行共转染表明，mGIF可抑制含TATA启动子以及无TATA启动子的转录。这些观察结果表明，锌指转录因子mGIF可能在介导GDNF的某些生物学效应中起重要作用。
