Lee N T, Nayfeh S N, Chae C B
Department of Biochemistry, University of North Carolina, Chapel Hill 27599-7260.
J Biol Chem. 1989 May 5;264(13):7523-30.
We have investigated the mechanism of stimulation of thyroglobulin gene expression by thyrotropin (TSH) and cAMP in rat thyroid FRTL-5 cells. In contrast to the c-fos gene, induction of the thyroglobulin gene by TSH or cAMP is slow (10 h) and sensitive to cycloheximide treatment. We have identified a TSH and cAMP-responsive region of thyroglobulin gene between - 171 and - 140 base pairs from the transcription initiation site. The hormone-responsive region contains DNA sequence elements similar to the consensus cAMP-responsive element as well as the transcription factor AP-1-binding site but with opposite sequence polarity. Three DNA-protein complexes are formed when the hormone-responsive region is incubated with nuclear extracts of FRTL-5 cells. Formation of these complexes is dependent on TSH or cAMP stimulation, thus suggesting that the factors involved in binding to the hormone-responsive region may be induced by TSH. Although the identity of these factors is not yet known, they do not appear to be related to either cAMP-responsive element-binding protein or AP-1. These results suggest that thyroglobulin gene expression in FRTL-5 cells may be mediated by nuclear factors that are induced by cAMP in contrast to other genes (e.g. c-fos) whose activation involves post-translational modification of the pre-existing proteins specific for cAMP-responsive element.
我们研究了促甲状腺激素（TSH）和环磷酸腺苷（cAMP）在大鼠甲状腺FRTL-5细胞中刺激甲状腺球蛋白基因表达的机制。与c-fos基因不同，TSH或cAMP诱导甲状腺球蛋白基因的过程缓慢（10小时），且对放线菌酮处理敏感。我们在转录起始位点上游-171至-140碱基对之间鉴定出了甲状腺球蛋白基因的TSH和cAMP反应区域。该激素反应区域包含与共有cAMP反应元件相似的DNA序列元件以及转录因子AP-1结合位点，但序列极性相反。当激素反应区域与FRTL-5细胞的核提取物一起孵育时，会形成三种DNA-蛋白质复合物。这些复合物的形成依赖于TSH或cAMP刺激，因此表明与激素反应区域结合的因子可能由TSH诱导。尽管这些因子的身份尚不清楚，但它们似乎与cAMP反应元件结合蛋白或AP-1均无关。这些结果表明，与其他基因（如c-fos）不同，FRTL-5细胞中甲状腺球蛋白基因的表达可能由cAMP诱导的核因子介导，c-fos基因的激活涉及对cAMP反应元件特异性的现有蛋白质进行翻译后修饰。
