Janknecht R, Nordheim A
Institute for Molecular Biology, Hannover Medical School, Germany.
Biochem Biophys Res Commun. 1996 Nov 21;228(3):831-7. doi: 10.1006/bbrc.1996.1740.
A plethora of signals induce the c-fos proto-oncogene via phosphorylation of the transcription factor Elk-1 by MAP kinase. We show that the coactivator CBP cooperates with Elk-1 to stimulate c-fos. Elk-1 physically interacts with CBP, which is dependent on the transactivation domain of Elk-1 but is independent of MAP kinase phosphorylation. However, functional cooperation between Elk-1 and CBP requires phosphorylation of Elk-1. Importantly, a carboxy-terminal transactivation domain of CBP itself is phosphorylated by MAP kinase, whereby the transactivation potential of CBP is enhanced. Thus, MAP kinase may not solely activate specific transcription factors but also the coactivator CBP, identifying a novel aspect of MAP kinase function. Thereby MAP kinase stimulation can pleiotropically affect activation of genes regulated by different transcription factors interacting with the same coactivator CBP.
大量信号通过丝裂原活化蛋白激酶（MAP激酶）对转录因子Elk-1进行磷酸化来诱导c-fos原癌基因。我们发现辅激活因子CBP与Elk-1协同作用以刺激c-fos。Elk-1与CBP发生物理相互作用，这依赖于Elk-1的反式激活结构域，但独立于MAP激酶磷酸化。然而，Elk-1与CBP之间的功能协同需要Elk-1的磷酸化。重要的是，CBP自身的羧基末端反式激活结构域被MAP激酶磷酸化，从而增强了CBP的反式激活潜能。因此，MAP激酶可能不仅激活特定转录因子，还激活辅激活因子CBP，这揭示了MAP激酶功能的一个新方面。由此，MAP激酶刺激可多效性地影响由与同一辅激活因子CBP相互作用的不同转录因子调控的基因的激活。
