Subramaniam M, Harris S A, Oursler M J, Rasmussen K, Riggs B L, Spelsberg T C
Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Nucleic Acids Res. 1995 Dec 11;23(23):4907-12. doi: 10.1093/nar/23.23.4907.
The TGF-beta family of growth factors has been extensively studied and found to play major roles in bone physiology and disease. A novel, TGF-beta-inducible early gene (TIEG) in normal human fetal osteoblasts (hFOB) has been identified using differential-display PCR. Using this differentially expressed cDNA fragment of TIEG to screen a hOB cDNA library, a near full-length cDNA for this gene was isolated. Northern analyses indicated that the steady-state levels of the 3.5 kb TIEG mRNA increased within 30 min of TGF-beta treatment of human osteoblasts and reached a maximum of 10-fold above control levels at 120 min post-treatment. This regulation was independent of new protein synthesis. Computer sequence analyses indicates that TIEG mRNA encodes for a 480 amino-acid protein. The TIEG protein contains three zinc finger motifs, several proline-rich src homology-3 (SH3) binding domains at the C-terminal end, and is homologous in this region to the zinc finger-containing transcription factor family of genes. A growth factor/cytokine-specific induction of TIEG has been shown. TIEG expression in hFOB cells was highly induced by TGF-beta and bone morphogenetic protein-2 (BMP-2), with a moderate induction by epidermal growth factor (EGF), but no induction by other growth factors/cytokines was observed. In addition to osteoblastic cells, high levels of TIEG expression were detected in skeletal muscle tissue, while low or no detectable levels were found in brain, lung, liver or kidney. Because TIEG is an early induced putative transcription factor gene, and shows a growth factor induction and tissue specificity, its protein product might play an important role as a signalling molecule in osteoblastic cells.
转化生长因子-β（TGF-β）家族的生长因子已得到广泛研究，并发现其在骨骼生理和疾病中发挥着重要作用。利用差异显示PCR技术，在正常人类胎儿成骨细胞（hFOB）中鉴定出一种新的、TGF-β诱导早期基因（TIEG）。利用该差异表达的TIEG cDNA片段筛选hOB cDNA文库，分离出该基因的近全长cDNA。Northern分析表明，TGF-β处理人成骨细胞30分钟内，3.5 kb的TIEG mRNA稳态水平升高，处理后120分钟达到对照水平的最高10倍。这种调节与新蛋白质合成无关。计算机序列分析表明，TIEG mRNA编码一种480个氨基酸的蛋白质。TIEG蛋白包含三个锌指基序，在C末端有几个富含脯氨酸的src同源-3（SH3）结合结构域，并且在该区域与含锌指的转录因子基因家族同源。已显示TIEG受生长因子/细胞因子特异性诱导。在hFOB细胞中，TIEG表达受到TGF-β和骨形态发生蛋白-2（BMP-2）的高度诱导，受到表皮生长因子（EGF）的中度诱导，但未观察到其他生长因子/细胞因子的诱导作用。除成骨细胞外，在骨骼肌组织中检测到高水平的TIEG表达，而在脑、肺、肝或肾中发现低水平或未检测到的水平。由于TIEG是一个早期诱导的假定转录因子基因，并表现出生长因子诱导和组织特异性，其蛋白质产物可能作为成骨细胞中的信号分子发挥重要作用。
