Adenovirus E1A products activate the Ig k-chain enhancer in fibroblasts. A possible involvement of the NF-kB binding site

Abstract

Proteins encoded by the early region 1A (E1A) regulate transcription of viral and cellular genes. The mechanism of this trans-regulation remains unclear but it is of considerable interest as an example of transcription regulation through cellular intermediates. We have therefore studied the effect of E1A products on the activity of the k-L chain gene enhancer. In our previous studies we have found that the k-chain enhancer is activated by E1A products in fibroblasts. Using in vivo competition experiments we found that the E1A regulatory effect involves trans-acting factors that can be titrated out by the k-chain enhancer sequences. Our transfection experiments suggest that the k3 enhancer fragment, encompassing the NF-kB binding site, is one of the sites through which the adenovirus E1A products exert their transactivation effect. The level of the nuclear factors that bind to the NF-kB binding site increases in fibroblasts that constitutively express E1A products. Understanding the mechanisms through which E1A regulates transcription should help to illuminate cellular mechanisms of gene control in normal and transformed cells.