Four isoforms of serum response factor that increase or inhibit smooth-muscle-specific promoter activity
Four isoforms of serum response factor that increase or inhibit smooth-muscle-specific promoter activity
复制标题
DOI：
10.1042/0264-6021:3450445
复制
发表时间：
2000-02-01
影响因子：
4.1
通讯作者：
Metcalfe, JC
中科院分区：
文献类型：
--
作者：
Kemp, PR;Metcalfe, JC
血清反应因子(SRF)是c-fos基因和肌肉特异性基因表达的关键转录激活因子。我们已经鉴定了SRF编码序列的四种形式：SRF-L(先前确定的形式)、SRF-M、SRF-S和SRF-I，它们是通过选择性剪接产生的。新形式的SRF通过剪接外显子5(SRF-M)、外显子4和5(SRF-S)和外显子3、4和5(SRF-I)而缺少C末端反式激活结构域。在分化的血管平滑肌细胞和骨骼肌细胞中，SRF-M的表达水平与SRF-L相似，而在许多其他组织中，SRF-M是主要的表达形式。SRF-S的表达仅限于血管平滑肌，SRF-I的表达仅限于胚胎。将SRF-L和SRF-M导入C2C12细胞，发现两种形式的SRF都是Sm22α基因启动子的反式激活因子，而SRF-I则是SRF的主要负性形式。
Serum response factor (SRF) is a key transcriptional activator of the c-fos gene and of muscle-specific gene expression. We have identified four forms of the SRF coding sequence, SRF-L (the previously identified form), SRF-M, SRF-S and SRF-I, that are produced by alternative splicing. The new forms of SRF lack regions of the C-terminal transactivation domain by splicing out of exon 5 (SRF-M), exons 4 and 5 (SRF-S) and exons 3, 4 and 5 (SRF-I). SRF-M is expressed at similar levels to SRF-L in differentiated vascular smooth-muscle cells and skeletal-muscle cells, whereas SRF-L is the predominant form in many other tissues. SRF-S expression is restricted to vascular smooth muscle and SRF-I expression is restricted to the embryo. Transfection of SRF-L and SRF-M into C2C12 cells showed that both forms are transactivators of the promoter of the smooth-muscle-specific gene SM22 alpha, whereas SRF-I acted as a dominant negative form of SRF.