Lin Y S, Green M R
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Nature. 1989 Aug 24;340(6235):656-9. doi: 10.1038/340656a0.
Organisms as diverse as bacteria and man contain genes that show transcriptional induction when the intracellular concentration of cAMP is increased. This regulated transcriptional response is mediated through specific promoter elements located, in general, upstream from the transcription start site. In Escherichia coli the element responsible for cAMP-mediated transcriptional induction is the binding site for the cAMP-receptor protein (CAP). In mammalian cells the cAMP regulatory element is composed of one or more binding sites for various transcription factors. In many instances the cAMP regulatory element contains binding sites for a family of proteins referred to as ATF. Here we provide evidence that some prokaryotic and mammalian cAMP-response elements are functionally related. First, we show that mammalian ATF binds specifically to some E. coli CAP sites, and conversely E. coli CAP binds specifically to some mammalian ATF sites. Second, we demonstrate that an E. coli CAP binding site can confer cAMP-inducibility onto a mammalian gene when assayed in transfected mammalian cells.
像细菌和人类这样差异巨大的生物体都含有一些基因,当细胞内cAMP浓度升高时,这些基因会表现出转录诱导。这种受调控的转录反应通常是通过位于转录起始位点上游的特定启动子元件介导的。在大肠杆菌中,负责cAMP介导的转录诱导的元件是cAMP受体蛋白(CAP)的结合位点。在哺乳动物细胞中,cAMP调节元件由一个或多个各种转录因子的结合位点组成。在许多情况下,cAMP调节元件包含一个被称为ATF的蛋白质家族的结合位点。在这里,我们提供证据表明一些原核生物和哺乳动物的cAMP反应元件在功能上是相关的。首先,我们表明哺乳动物的ATF能特异性地结合一些大肠杆菌的CAP位点,反之,大肠杆菌的CAP也能特异性地结合一些哺乳动物的ATF位点。其次,我们证明,当在转染的哺乳动物细胞中进行检测时,一个大肠杆菌的CAP结合位点可以赋予一个哺乳动物基因cAMP诱导性。