Zhou Q, Engel D A
Department of Microbiology and Cancer Center, University of Virginia School of Medicine, Charlottesville 22908, USA.
J Virol. 1995 Dec;69(12):7402-9. doi: 10.1128/JVI.69.12.7402-7409.1995.
The adenovirus E1A243 protein can activate transcription of the mouse c-fos gene in a manner that depends on treatment of cells with inducers or analogs of cyclic AMP (cAMP). Activation requires conserved region 1 and the N-terminal domain of E1A243 and is mediated by a 22-bp E1A response element containing a cAMP response element (CRE) at -67 and a binding site for transcription factor YY1 at -54. In the absence of E1A243, YY1 represses CRE-dependent transcription of c-fos by physically interacting with ATF/CREB proteins bound to the -67 CRE. Here we present evidence that expression of E1A243 leads to relief of YY1-mediated repression by a disruption of the ATF/CREB-YY1 complex. Addition of E1A243 to in vitro binding assays prevented binding of ATF-2 to glutathione S-transferase-YY1. Similarly, expression of E1A243 in HeLa cells prevented the association of a YY1-VP16 fusion protein with endogenous ATF/CREB proteins bound to the -67 CRE of a transfected c-fosCAT reporter plasmid. In each case, the N-terminal domain of E1A243, which mediates a direct interaction with YY1, was responsible for disruption of the ATF/CREB-YY1 complex. On the basis of these and previously published results, we present a model for the synergistic transcriptional activation of the c-fos gene by E1A243 and cAMP.
腺病毒E1A243蛋白能够以一种依赖于用环磷酸腺苷（cAMP）诱导剂或类似物处理细胞的方式激活小鼠c-fos基因的转录。激活需要E1A243的保守区域1和N端结构域，并且由一个22碱基对的E1A反应元件介导，该元件在-67处含有一个cAMP反应元件（CRE），在-54处含有转录因子YY1的结合位点。在没有E1A243的情况下，YY1通过与结合在-67 CRE上的ATF/CREB蛋白进行物理相互作用来抑制c-fos的CRE依赖性转录。在此我们提供证据表明，E1A243的表达通过破坏ATF/CREB-YY1复合物导致YY1介导的抑制作用解除。在体外结合试验中加入E1A243可阻止ATF-2与谷胱甘肽S-转移酶-YY1结合。同样，在HeLa细胞中表达E1A243可阻止YY1-VP16融合蛋白与结合在转染的c-fosCAT报告质粒-67 CRE上的内源性ATF/CREB蛋白结合。在每种情况下，介导与YY1直接相互作用的E1A243的N端结构域负责破坏ATF/CREB-YY1复合物。基于这些以及先前发表的结果，我们提出了一个关于E1A243和cAMP协同转录激活c-fos基因的模型。
