Two pathways for serum regulation of the c-fos serum response element require specific sequence elements and a minimal domain of serum response factor.
Two pathways for serum regulation of the c-fos serum response element require specific sequence elements and a minimal domain of serum response factor.
复制标题
c-fos 血清反应元件的血清调节的两种途径需要特定的序列元件和血清反应因子的最小结构域。
DOI：
10.1128/mcb.14.9.5920-5928.1994
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发表时间：
1994
影响因子：
5.3
通讯作者：
Prywes,R
中科院分区：
文献类型：
--
作者：
Johansen,FE;Prywes,R
c-fosserum应答元件（SRE）是诱导c-fosgene应答血清和生长因子所必需和充分的。这种激活依赖于血清反应因子（SRF），一种结合SRE的转录激活因子。一种与SRF结合到SRE并被促分裂原活化蛋白激酶激活的因子p62 TCF也与c-fos调节有关。通过使用具有弱SRE突变的报告基因系统（其依赖于SRF的过表达用于血清诱导），我们发现存在至少两种会聚于SRE的血清诱导途径。SRF和SRE突变导致的TCF结合丧失并没有减少报告基因的血清诱导。我们已经发现了一种血清诱导途径，该途径对SRE的含A/T的中心序列中的突变敏感，并且不依赖于TCF。当该途径突变时，激活依赖于TCF结合，表明TCF也可以在血清诱导中起作用。这两种信号通路都需要SRF的最小结构域。该结构域跨越SRF的DNA结合结构域，当与异源转录激活结构域融合时足以用于血清诱导。
The c-fosserum response element (SRE) is necessary and sufficient for induction of the c-fosgene in response to serum and growth factors. This activation is dependent upon serum response factor (SRF), a transcriptional activator which binds the SRE. A factor, p62TCF, which binds in conjunction with SRF to the SRE and which is activated by mitogen-activated protein kinase, has also been implicated in c-fosregulation. By using a reporter gene system with weak SRE mutations that is dependent upon overexpression of SRF for serum induction, we have found that there are at least two pathways for serum induction that converge on the SRE. Loss of TCF binding by mutations in SRF and the SRE did not reduce serum induction of the reporter genes. We have found a pathway for serum induction that is sensitive to mutations in the A/T-containing central sequence of the SRE and which is independent of TCF. When this pathway was mutated, activation was dependent upon TCF binding, demonstrating that TCF can also function in serum induction. Both of the signalling pathways required a minimal domain of SRF. This domain, spanning SRF's DNA binding domain, was sufficient for serum induction when fused to a heterologous transcriptional activation domain.