DIFFERENCE IN TRANSCRIPTIONAL REGULATORY FUNCTION BETWEEN C-FOS AND FRA-2
DIFFERENCE IN TRANSCRIPTIONAL REGULATORY FUNCTION BETWEEN C-FOS AND FRA-2
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DOI：
10.1093/nar/19.20.5537
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发表时间：
1991-10-25
影响因子：
14.9
通讯作者：
IBA, H
中科院分区：
文献类型：
--
作者：
SUZUKI, T;OKUNO, H;IBA, H
Fos相关抗原Fra-2在成纤维细胞生长刺激后迅速表达，但其诱导高峰晚于c-Fos。在这份报告中，我们研究了Fra-2的生化特性，并将其与其他两种Fos家族蛋白c-Fos和Fra-1的生化特性进行了比较。与c-Fos和Fra-1一样，Fra-2与c-Jun、JunB或JunD在体外形成稳定的异源二聚体，这些复合物均具有与AP-1结合位点（AP-1 sites）或相关序列的特异性DNA结合活性。当瞬时引入到小鼠胚胎癌细胞系，F9，与报告基因含有AP-1位点的胶原酶基因，fra-2加c-jun抑制c-jun单独的反式激活。Fra-2的这种性质与c-Fos形成鲜明对比，c-Fos通过形成稳定的异源二聚体来刺激c-Jun的转录活性。对c-Fos和Fra-2嵌合蛋白的分析表明，这种差异主要归因于它们的C端半区。有趣的是，Fra-2的这种抑制作用在与junD的组合中没有观察到：与c-fos加junD一样，fra-2加junD比单独的junD具有更高的转录活性。Fra-1显示出与Fra-2基本相同的转录调控特性。这些差异性极大地扩展了Fos家族蛋白的潜在调节功能范围。
Fra-2, one of the Fos-related antigens, is promptly expressed after the growth stimulation of fibroblasts, but its induction peak is later than that of c-Fos. In this report, we examined biochemical properties of Fra-2 and compared them with those of two other Fos family proteins, c-Fos and Fra-1. Like c-Fos and Fra-1, Fra-2 formed stable heterodimers with c-Jun, JunB or JunD in vitro and all these complexes had specific DNA-binding activity to AP-1-binding sites (AP-1 sites) or related sequences. When transiently introduced into a mouse embryonic carcinoma cell line, F9, with reporter genes containing the AP-1 site from the collagenase gene, fra-2 plus c-jun suppressed the transactivation by c-jun alone. This property of Fra-2 is in clear contrast to that of c-Fos, which stimulates the transcriptional activity of c-Jun by forming a stable heterodimer. Analysis of chimeric proteins between c-Fos and Fra-2 indicated that this difference is mainly attributable to their C terminal-half regions. Interestingly, this suppressive effect of Fra-2 was not observed in the combination with JunD: fra-2 plus junD, like c-fos plus junD, had higher transcriptional activity than junD alone. Fra-1 showed essentially the same transcriptional regulatory properties as Fra-2. These differential properties greatly expand the potential range of regulatory functions of the Fos family proteins.