SERUM-REGULATED TRANSCRIPTION BY SERUM-RESPONSE-FACTOR (SRF) - A NOVEL ROLE FOR THE DNA-BINDING DOMAIN
SERUM-REGULATED TRANSCRIPTION BY SERUM-RESPONSE-FACTOR (SRF) - A NOVEL ROLE FOR THE DNA-BINDING DOMAIN
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DOI：
10.1002/j.1460-2075.1994.tb06877.x
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发表时间：
1994-11-15
期刊：
影响因子：
11.4
通讯作者：
TREISMAN, R
中科院分区：
文献类型：
--
作者：
HILL, CS;WYNNE, J;TREISMAN, R
转录因子血清反应因子(SRF)和三元复合因子(TCF)在c-fos血清反应元件(SRE)处形成三元复合体。我们发现，在NIH3T3细胞中，TCF结合是调控转录所必需的，以响应佛波酯(PMA)的刺激，而不是全血清。我们构建了一个新的转录失活的SRE变异体，在没有结合的TCF的情况下，其血清调节的活性可以通过过表达SRF来部分恢复。SRF的激活不需要SRF N端的磷酸化位点，但被SRF C端的激活结构域增强了2-3倍。SRF DNA结合域的突变不会影响SRF与DNA的结合能力，从而丧失了其介导TCF非依赖血清调节的激活的能力，并减少了SRF/TCF(Elk-1)三元复合体的激活。有效的激活需要SRF通过其自身的DNA结合域靶向DNA。
The transcription factors Serum Response Factor (SRF) and Ternary Complex Factor (TCF) form a ternary complex at the c-fos Serum Response Element (SRE). We show that in NIH3T3 cells TCF binding is required for regulated transcription in response to stimulation by phorbol myristate acetate (PMA), but not by whole serum. We constructed a novel transcriptionally inactive SRE variant whose serum-regulated activity can be partially restored by overexpression of SRF in the absence of bound TCF. Activation by SRF does not require the SRF N-terminal phosphorylation sites, but is potentiated 2- to 3-fold by the SRF C-terminal activation domain. Mutations in the SRF DNA binding domain, which do not affect the ability of SRF to bind DNA, abolish its ability to mediate TCF-independent serum-regulated activation and reduce activation by the SRF/TCF(Elk-1) ternary complex. Efficient activation requires that SRF be targeted to DNA via its own DNA binding domain.