Gille H, Kortenjann M, Strahl T, Shaw P E
Spemann Laboratories, Max-Planck-Institut für Immunbiologie, Freiburg,Germany.
Mol Cell Biol. 1996 Mar;16(3):1094-102. doi: 10.1128/MCB.16.3.1094.
The rapid and transient induction of the human proto-oncogene c-fos in response to a variety of stimuli depends on the serum responses element (SRE). In vivo footprinting experiments show that this promoter element is bound by a multicomponent complex including the serum response factor (SRF) and a ternary complex factor such as Elk-1. SRF is thought to recruit a ternary complex factor monomer into an asymmetric complex. In this report, we describe a quaternary complex over the SRE which, in addition to an SRF dimer, contains two Elk-1 molecules. Its formation at the SRE is strictly dependent on phosphorylation of S-383 in the Elk-1 regulatory domain and appears to involve a weak intermolecular association between the two Elk-1 molecules. The influence of mutations in Elk-1 on quaternary complex formation in vitro correlates with their effect on the induction of c-fos reporter expression in response to mitogenic stimuli in vivo.
人类原癌基因c-fos对多种刺激的快速和短暂诱导依赖于血清反应元件(SRE)。体内足迹实验表明,该启动子元件由一个多组分复合物结合,该复合物包括血清反应因子(SRF)和一个三元复合物因子,如Elk-1。SRF被认为将一个三元复合物因子单体招募到一个不对称复合物中。在本报告中,我们描述了一种在SRE上形成的四元复合物,除了一个SRF二聚体外,还包含两个Elk-1分子。它在SRE处的形成严格依赖于Elk-1调节域中S-383的磷酸化,并且似乎涉及两个Elk-1分子之间的弱分子间缔合。Elk-1中的突变对体外四元复合物形成的影响与其对体内有丝分裂刺激响应的c-fos报告基因表达诱导的影响相关。