Repression of c-Jun-induced mouse major histocompatibility class I promoter (H-2Kb) activity by the Adenovirus type 12-unique 52R E1A protein

Abstract

Down-regulation of major histocompatibility (MHC) class I gene expression by protein products of the early region 1A (E1A), which might allow transformed cells to escape the host immune system, is discussed as one cause for the oncogenicity of Adenovirus (Ad) subtype 12-transformed cells. The MHC class I promoter is activated through several cellular-transcription factors among them AP-1, whose target sequences are located in the enhancers A and B, and NF kappa B. In this report we present evidence that the Ad12-unique 52R E1A protein inhibits c-Jun-induced activation of MHC class I gene expression. Repression occurs through both AP-1 recognition sequences with the AP-1 binding site of Enhancer A, which can be bound by c-Jun dimers in vitro, being the main target for c-Jun activation as well as 52R-mediated down-regulation. Furthermore our data revealed that both promoter elements of Enhancer A, the AP-1 and NF kappa B binding sites, are necessary for full promoter activity. As NF kappa B is down-regulated by the 266R protein of Ad12 E1A our results suggest a model in which two Ad12 E1A proteins co-operate in the repression of MHC class I gene expression.