ETS-RELATED PROTEIN ELK-1 IS HOMOLOGOUS TO THE C-FOS REGULATORY FACTOR P62TCF
ETS-RELATED PROTEIN ELK-1 IS HOMOLOGOUS TO THE C-FOS REGULATORY FACTOR P62TCF
复制标题
DOI：
10.1038/354531a0
复制
发表时间：
1991-12-19
期刊：
影响因子：
64.8
通讯作者：
NORDHEIM, A
中科院分区：
文献类型：
--
作者：
HIPSKIND, RA;RAO, VN;NORDHEIM, A
在细胞对增殖信号的反应中，一个关键事件是c-fos原癌基因的快速、瞬时诱导，这是通过fos启动子1-4中的血清反应元件(SRE)介导的。基因组足迹5，6和转染实验7-9表明，这种激活是通过一个三元复合体发生的，它包括血清反应因子(SRF)10和三元复合体因子p62(参考文献7-9)。7)。P62TCF与SRF-SRE二元复合体的相互作用需要一个紧邻SRE上游的CAGGA区(参考文献)。7)。Ets原癌基因家族的蛋白质与相似的序列11-13结合，我们发现该家族的成员Elk-1(参考文献)。14)，与SRE形成依赖于SRF的三元配合物。ELK-1和p62TCF具有相同的DNA序列要求，抗ELK-1的抗体阻断了这两种蛋白的结合。此外，我们发现与P62TCF一样，ELK-1与酵母SRF同源物MCM1形成复合体，但不与酵母ARG80形成复合体(参考文献1)。15)。但与p62TCF相互作用的ARG80突变体也可以与ELK-1形成复合体。ELK-1和p62TCF之间的相似性甚至同一性表明了ETS蛋白的一种新的调节作用，这种作用是通过与其他蛋白质的相互作用来实现的，例如SRF。此外，ETS蛋白可能参与了c-fos的调控，这对原癌基因在细胞生长控制中的合作具有有趣的意义。
A KEY event in the response of cells to proliferative signals is the rapid, transient induction of the c-fos proto-oncogene, which is mediated through the serum response element (SRE) in the fos promoter 1-4. Genomic footprinting 5,6 and transfection experiments 7-9 suggest that this activation occurs through a ternary complex that includes the serum response factor (SRF) 10 and the ternary complex factor p62 (ref. 7). Interaction of p62TCF with the SRF-SRE binary complex requires a CAGGA tract immediately upstream of the SRE (ref. 7). Proteins of the ets proto-oncogene family bind to similar sequences 11-13 and we have found that a member of this family, Elk-1 (ref. 14), forms SRF-dependent ternary complexes with the SRE. Elk-1 and p62TCF have the same DNA sequence requirements and antibodies against Elk-1 block the binding of both proteins. Furthermore, we show that like P62TCF, Elk-1 forms complexes with the yeast SRF-homologue MCM1 but not with yeast ARG80 (ref. 15). But ARG80 mutants that convey interaction with p62TCF can also form complexes with Elk-1. The similarity, or even identity, between Elk-1 and p62TCF suggests a novel regulatory role for Ets proteins that is effected through interaction with other proteins, such as SRF. Furthermore, the possible involvement of an Ets protein in the control of c-fos has interesting implications for proto-oncogene cooperation in cellular growth control 16.